RESUMO
Intellectual disability (ID) is a measurable phenotypic consequence of genetic and environmental factors. In this study, we prospectively assessed the diagnostic yield of genomic tools (molecular karyotyping, multi-gene panel and exome sequencing) in a cohort of 337 ID subjects as a first-tier test and compared it with a standard clinical evaluation performed in parallel. Standard clinical evaluation suggested a diagnosis in 16% of cases (54/337) but only 70% of these (38/54) were subsequently confirmed. On the other hand, the genomic approach revealed a likely diagnosis in 58% (n=196). These included copy number variants in 14% (n=54, 15% are novel), and point mutations revealed by multi-gene panel and exome sequencing in the remaining 43% (1% were found to have Fragile-X). The identified point mutations were mostly recessive (n=117, 81%), consistent with the high consanguinity of the study cohort, but also X-linked (n=8, 6%) and de novo dominant (n=19, 13%). When applied directly on all cases with negative molecular karyotyping, the diagnostic yield of exome sequencing was 60% (77/129). Exome sequencing also identified likely pathogenic variants in three novel candidate genes (DENND5A, NEMF and DNHD1) each of which harbored independent homozygous mutations in patients with overlapping phenotypes. In addition, exome sequencing revealed de novo and recessive variants in 32 genes (MAMDC2, TUBAL3, CPNE6, KLHL24, USP2, PIP5K1A, UBE4A, TP53TG5, ATOH1, C16ORF90, SLC39A14, TRERF1, RGL1, CDH11, SYDE2, HIRA, FEZF2, PROCA1, PIANP, PLK2, QRFPR, AP3B2, NUDT2, UFC1, BTN3A2, TADA1, ARFGEF3, FAM160B1, ZMYM5, SLC45A1, ARHGAP33 and CAPS2), which we highlight as potential candidates on the basis of several lines of evidence, and one of these genes (SLC39A14) was biallelically inactivated in a potentially treatable form of hypermanganesemia and neurodegeneration. Finally, likely causal variants in previously published candidate genes were identified (ASTN1, HELZ, THOC6, WDR45B, ADRA2B and CLIP1), thus supporting their involvement in ID pathogenesis. Our results expand the morbid genome of ID and support the adoption of genomics as a first-tier test for individuals with ID.
Assuntos
Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Variações do Número de Cópias de DNA , Exoma/genética , Feminino , Genômica , Humanos , Deficiência Intelectual/metabolismo , Cariotipagem/métodos , Masculino , Mutação , Estudos Prospectivos , Sensibilidade e Especificidade , Análise de Sequência de DNA/métodos , Adulto JovemRESUMO
Personalized or precision medicine is predicated on the assumption that the average response to treatment is not necessarily representative of the response of each individual. A commitment to personalized medicine demands an effort to bring evidence-based medicine and personalized medicine closer together. The use of relatively homogeneous groups, defined using a priori criteria, may constitute a promising initial step for developing more accurate risk-prediction models with which to advance the development of personalized evidence-based medicine approaches to heterogeneous syndromes such as schizophrenia. However, this can lead to a paradoxical situation in the field of psychiatry. Since there has been a tendency to loosely define psychiatric disorders as ones without a known aetiology, the discovery of an aetiology for psychiatric syndromes (e.g. 22q11.2 deletion syndrome in some cases of schizophrenia), while offering a path toward more precise treatments, may also lead to their reclassification away from psychiatry. We contend that psychiatric disorders with a known aetiology should not be removed from the field of psychiatry. This knowledge should be used instead to guide treatment, inasmuch as psychotherapies, pharmacotherapies and other treatments can all be valid approaches to mental disorders. The translation of the personalized clinical approach inherent to psychiatry into evidence-based precision medicine can lead to the development of novel treatment options for mental disorders and improve outcomes.
Assuntos
Transtornos Mentais/terapia , Medicina de Precisão/normas , Psiquiatria/normas , Humanos , Transtornos Mentais/etiologia , Medicina de Precisão/métodos , Psiquiatria/métodosRESUMO
An increasing number of genetic variants have been implicated in autism spectrum disorders (ASDs), and the functional study of such variants will be critical for the elucidation of autism pathophysiology. Here, we report a de novo balanced translocation disruption of TRPC6, a cation channel, in a non-syndromic autistic individual. Using multiple models, such as dental pulp cells, induced pluripotent stem cell (iPSC)-derived neuronal cells and mouse models, we demonstrate that TRPC6 reduction or haploinsufficiency leads to altered neuronal development, morphology and function. The observed neuronal phenotypes could then be rescued by TRPC6 complementation and by treatment with insulin-like growth factor-1 or hyperforin, a TRPC6-specific agonist, suggesting that ASD individuals with alterations in this pathway may benefit from these drugs. We also demonstrate that methyl CpG binding protein-2 (MeCP2) levels affect TRPC6 expression. Mutations in MeCP2 cause Rett syndrome, revealing common pathways among ASDs. Genetic sequencing of TRPC6 in 1041 ASD individuals and 2872 controls revealed significantly more nonsynonymous mutations in the ASD population, and identified loss-of-function mutations with incomplete penetrance in two patients. Taken together, these findings suggest that TRPC6 is a novel predisposing gene for ASD that may act in a multiple-hit model. This is the first study to use iPSC-derived human neurons to model non-syndromic ASD and illustrate the potential of modeling genetically complex sporadic diseases using such cells.
Assuntos
Transtorno Autístico/patologia , Neurônios/patologia , Canais de Cátion TRPC/metabolismo , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/metabolismo , Transtorno Autístico/genética , Transtorno Autístico/fisiopatologia , Carboplatina/metabolismo , Diferenciação Celular/genética , Linhagem Celular , Proliferação de Células/genética , Células Cultivadas , Criança , Modelos Animais de Doenças , Embrião de Mamíferos , Etoposídeo/metabolismo , Regulação da Expressão Gênica/genética , Humanos , Técnicas In Vitro , Células-Tronco Pluripotentes Induzidas/fisiologia , Potenciais Pós-Sinápticos Inibidores/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mitoxantrona/metabolismo , Mutação/genética , Neurônios/metabolismo , Prednisolona/metabolismo , Transdução de Sinais/genética , Canais de Cátion TRPC/genética , Canal de Cátion TRPC6RESUMO
Copy number variants (CNVs) are risk factors in neurodevelopmental disorders, including autism, epilepsy, intellectual disability (ID) and schizophrenia. Childhood onset schizophrenia (COS), defined as onset before the age of 13 years, is a rare and severe form of the disorder, with more striking array of prepsychotic developmental disorders and abnormalities in brain development. Because of the well-known phenotypic variability associated with pathogenic CNVs, we conducted whole genome genotyping to detect CNVs and then focused on a group of 46 rare CNVs that had well-documented risk for adult onset schizophrenia (AOS), autism, epilepsy and/or ID. We evaluated 126 COS probands, 69 of which also had a healthy full sibling. When COS probands were compared with their matched related controls, significantly more affected individuals carried disease-related CNVs (P=0.017). Moreover, COS probands showed a higher rate than that found in AOS probands (P<0.0001). A total of 15 (11.9%) subjects exhibited at least one such CNV and four of these subjects (26.7%) had two. Five of 15 (4.0% of the sample) had a 2.5-3 Mb deletion mapping to 22q11.2, a rate higher than that reported for adult onset (0.3-1%) (P<0.001) or autism spectrum disorder and, indeed, the highest rate reported for any clinical population to date. For one COS subject, a duplication found at 22q13.3 had previously only been associated with autism, and for four patients CNVs at 8q11.2, 10q22.3, 16p11.2 and 17q21.3 had only previously been associated with ID. Taken together, these findings support the well-known pleiotropic effects of these CNVs suggesting shared abnormalities early in brain development. Clinically, broad CNV-based population screening is needed to assess their overall clinical burden.
Assuntos
Variações do Número de Cópias de DNA , Esquizofrenia Infantil/genética , Adulto , Criança , Transtornos Globais do Desenvolvimento Infantil/genética , Feminino , Pleiotropia Genética , Técnicas de Genotipagem , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Esquizofrenia/genética , Deleção de Sequência , IrmãosRESUMO
Copy number variants (CNVs) have a major role in the etiology of autism spectrum disorders (ASD), and several of these have reached statistical significance in case-control analyses. Nevertheless, current ASD cohorts are not large enough to detect very rare CNVs that may be causative or contributory (that is, risk alleles). Here, we use a tiered approach, in which clinically significant CNVs are first identified in large clinical cohorts of neurodevelopmental disorders (including but not specific to ASD), after which these CNVs are then systematically identified within well-characterized ASD cohorts. We focused our initial analysis on 48 recurrent CNVs (segmental duplication-mediated 'hotspots') from 24 loci in 31 516 published clinical cases with neurodevelopmental disorders and 13 696 published controls, which yielded a total of 19 deletion CNVs and 11 duplication CNVs that reached statistical significance. We then investigated the overlap of these 30 CNVs in a combined sample of 3955 well-characterized ASD cases from three published studies. We identified 73 deleterious recurrent CNVs, including 36 deletions from 11 loci and 37 duplications from seven loci, for a frequency of 1 in 54; had we considered the ASD cohorts alone, only 58 CNVs from eight loci (24 deletions from three loci and 34 duplications from five loci) would have reached statistical significance. In conclusion, until there are sufficiently large ASD research cohorts with enough power to detect very rare causative or contributory CNVs, data from larger clinical cohorts can be used to infer the likely clinical significance of CNVs in ASD.
Assuntos
Transtornos Globais do Desenvolvimento Infantil/genética , Dosagem de Genes , Transtorno Autístico/epidemiologia , Transtorno Autístico/genética , Causalidade , Transtornos Globais do Desenvolvimento Infantil/epidemiologia , Anormalidades Congênitas/epidemiologia , Anormalidades Congênitas/genética , Mineração de Dados , Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/genética , Deleção de Genes , Duplicação Gênica , Estudos de Associação Genética , Heterogeneidade Genética , Predisposição Genética para Doença , Recombinação Homóloga , Humanos , Prevalência , Tamanho da AmostraRESUMO
Tourette's syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association study (GWAS) of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel and French Canadians from Quebec, Canada. In a primary meta-analysis of GWAS data from these European ancestry samples, no markers achieved a genome-wide threshold of significance (P<5 × 10(-8)); the top signal was found in rs7868992 on chromosome 9q32 within COL27A1 (P=1.85 × 10(-6)). A secondary analysis including an additional 211 cases and 285 controls from two closely related Latin American population isolates from the Central Valley of Costa Rica and Antioquia, Colombia also identified rs7868992 as the top signal (P=3.6 × 10(-7) for the combined sample of 1496 cases and 5249 controls following imputation with 1000 Genomes data). This study lays the groundwork for the eventual identification of common TS susceptibility variants in larger cohorts and helps to provide a more complete understanding of the full genetic architecture of this disorder.
Assuntos
Colágenos Fibrilares/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único/genética , Síndrome de Tourette/genética , Adolescente , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Transtorno do Deficit de Atenção com Hiperatividade/genética , Estudos de Casos e Controles , Cromossomos Humanos Par 9/genética , Feminino , Genótipo , Humanos , Cooperação Internacional , Masculino , Metanálise como Assunto , Transtorno Obsessivo-Compulsivo/etiologia , Transtorno Obsessivo-Compulsivo/genética , Síndrome de Tourette/complicações , População Branca/genética , Adulto JovemRESUMO
In the last decade there has been a revolution in terms of genetic findings in neurodevelopmental disorders (NDDs), with many discoveries critical for understanding their aetiology and pathophysiology. Clinical trials in single-gene disorders such as fragile X syndrome highlight the challenges of investigating new drug targets in NDDs. Incorporating a developmental perspective into the process of drug development for NDDs could help to overcome some of the current difficulties in identifying and testing new treatments. This paper provides a summary of the proceedings of the 'New Frontiers Meeting' on neurodevelopmental disorders organised by the European College of Neuropsychopharmacology in conjunction with the Innovative Medicines Initiative-sponsored AIMS-2-TRIALS consortium. It brought together experts in developmental genetics, autism, NDDs, and clinical trials from academia and industry, regulators, patient and family associations, and other stakeholders. The meeting sought to provide a platform for focused communication on scientific insights, challenges, and methodologies that might be applicable to the development of CNS treatments from a neurodevelopmental perspective. Multidisciplinary translational consortia to develop basic and clinical research in parallel could be pivotal to advance knowledge in the field. Although implementation of clinical trials for NDDs in paediatric populations is widely acknowledged as essential, safety concerns should guide each aspect of their design. Industry and academia should join forces to improve knowledge of the biology of brain development, identify the optimal timing of interventions, and translate these findings into new drugs, allowing for the needs of users and families, with support from regulatory agencies.
Assuntos
Transtorno Autístico , Transtornos do Neurodesenvolvimento , Criança , Descoberta de Drogas/métodos , Humanos , Transtornos do Neurodesenvolvimento/tratamento farmacológico , Transtornos do Neurodesenvolvimento/genéticaAssuntos
Predisposição Genética para Doença/genética , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Polimorfismo de Nucleotídeo Único/genética , Síndrome de Tourette/genética , Regiões 3' não Traduzidas , Europa (Continente) , Predisposição Genética para Doença/etnologia , Estudo de Associação Genômica Ampla/métodos , Humanos , JudaísmoAssuntos
Malformação de Arnold-Chiari/complicações , Malformação de Arnold-Chiari/genética , Deleção Cromossômica , Cromossomos Humanos Par 5/genética , Síndrome da Retração Ocular/complicações , Síndrome da Retração Ocular/genética , Heterozigoto , Nervo Abducente/patologia , Variações do Número de Cópias de DNA/genética , Humanos , Masculino , Reação em Cadeia da Polimerase , Adulto JovemRESUMO
INTRODUCTION: Over the past years, there has been an increasing interest in involving the cancer patients in the decision making regarding the therapy management due to several factors. The most important aspect to be taken into consideration is the principle of patient autonomy. More and more patients have become interested in making informed decisions regarding their therapy options and physicians need to be able to provide data on the aspect. Some patient-physician models have been proposed and used for 40 years now. Still, the debate is very important for most of the physicians due to the shifts in the approach. MATERIALS AND METHODS: To really express the concerns that the authors address, the case of a head and neck cancer patient and the possible dialogues with the physician were presented. Each type of communication model with the patient is very important because nowadays, intrications between the four are likely to occur. There are legal aspects that need to be taken into consideration such as the informed consent, the ethical and moral aspects. CONCLUSIONS: The possibility of individualized oncological therapy for the cancer patient leads to different decisions for both the patient and the physician. The decision making process involves the patient at different levels. Legal implications tend to affect the healthiness of the dialogue between the physician and the cancer patient and might be a key-point in the further development of the ethical aspects.
Assuntos
Neoplasias/psicologia , Relações Médico-Paciente , Comunicação , Tomada de Decisões , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: This open, prospective study examined the effects of electroconvulsive therapy (ECT) in 10 adolescents with primary, endogenous, psychotic depression who were resistant to antidepressant pharmacotherapy. METHODS: Change in symptom severity from baseline was assessed weekly with Hamilton Depression Rating Scale (HDRS) ratings, and outcome was measured additionally at 1 month, and again at 1 year, post-ECT. RESULTS: All but 1 patient demonstrated dramatic improvement, with statistically significant decreases in mean HDRS score detected after the first week of treatment. All responders maintained the benefits of their treatment. CONCLUSIONS: The results provide evidence of the clinical effectiveness of ECT in adolescents with phenomenological characteristics shown to be predictive of ECT response in adults.
Assuntos
Transtorno Depressivo/terapia , Eletroconvulsoterapia , Adolescente , Antidepressivos/uso terapêutico , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/psicologia , Resistência a Medicamentos , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Resultado do TratamentoRESUMO
BACKGROUND: Prader-Willi syndrome (PWS) is a genetic disorder characterized by mental retardation, appetite dysregulation, and a high risk for obsessive-compulsive disorder (OCD). Microscopic abnormalities of the hypothalamus have been described in PWS, and oxytocin has been implicated in both appetite regulation and OCD. METHODS: Oxytocin and arginine vasopressin (AVP) were measured in the cerebrospinal fluid of 5 subjects with PWS (2 male, 3 female) and in 6 normal control subjects (all female). RESULTS: CSF oxytocin was elevated in PWS (9.2 +/- 3.9 pmol/L) as compared to normal control subjects (5.1 +/- 0.9 pmol/L, p = 0.045), a finding that was more significant when excluding male subjects from analysis (p = 0.02). AVP was not significantly different between the groups as a whole. CONCLUSIONS: These data provide further evidence for hypothalamic and oxytocinergic dysfunction in PWS. The associations between oxytocin, appetite regulation, and obsessive compulsive symptomatology in PWS warrant further investigation.
Assuntos
Ocitocina/líquido cefalorraquidiano , Síndrome de Prader-Willi/líquido cefalorraquidiano , Adolescente , Adulto , Arginina Vasopressina/líquido cefalorraquidiano , Feminino , Humanos , Masculino , Valores de Referência , Caracteres SexuaisRESUMO
OBJECTIVE: To review the literature over the past decade on mental retardation, particularly with respect to genetics and behavioral phenotypes. METHOD: A computerized search was performed for articles published in the past decade, and selected papers were highlighted. RESULTS: The study of mental retardation has benefited considerably by advances in medicine generally, and by developments in molecular neurobiology in particular. These advances in genetics have led to new insights regarding the causes of mental retardation, as well as a growing appreciation of behavioral phenotypes associated with some mental retardation syndromes. CONCLUSIONS: Although the study of developmental disorders has advanced significantly over the past decade, considerable work remains. Mental retardation should remain the model for the utility of the biopsychosocial approach in medicine.
Assuntos
Deficiência Intelectual/reabilitação , Adolescente , Criança , Terapia Combinada , Síndrome de Down/genética , Síndrome de Down/psicologia , Síndrome de Down/reabilitação , Síndrome do Cromossomo X Frágil/genética , Síndrome do Cromossomo X Frágil/psicologia , Síndrome do Cromossomo X Frágil/reabilitação , Humanos , Deficiência Intelectual/genética , Deficiência Intelectual/psicologia , Fenótipo , Síndrome de Prader-Willi/genética , Síndrome de Prader-Willi/psicologia , Síndrome de Prader-Willi/reabilitação , Prognóstico , Psicopatologia , Síndrome de Williams/genética , Síndrome de Williams/psicologia , Síndrome de Williams/reabilitaçãoRESUMO
OBJECTIVE: To review the literature over the past decade on the genetics of childhood neuropsychiatric disorders. METHOD: A computerized search was performed for articles published in the past decade, and selected papers were highlighted. RESULTS: The past decade of research has illuminated the complex genetics of early-onset mental disorders. Advances in statistical methodologies and laboratory-based gene-hunting techniques are laying the foundation for a deeper understanding of both the biological and environmental factors that contribute to mental illness. Researchers are on the verge of identifying and characterizing genetic vulnerabilities involved in common childhood psychiatric syndromes. CONCLUSIONS: Although the study of the genetics of childhood psychiatric disorders has advanced significantly over the past decade, considerable work remains. The identification of genes conferring vulnerability to psychiatric illnesses will have the potential to transform the field by providing insight into both biological and environmental determinants that contribute to serious developmental and psychiatric disorders in children and adolescents. These advances promise new understanding and new avenues for prevention and treatment. They will also present physicians and families with significant clinical and ethical challenges.
Assuntos
Mapeamento Cromossômico/métodos , Predisposição Genética para Doença/genética , Transtornos Mentais/genética , Mutação , Criança , Regulação da Expressão Gênica , Genótipo , Humanos , Fenótipo , SíndromeRESUMO
OBJECTIVE: To review the literature over the past decade on mental retardation, particularly as regards its definition, prevalence, major causes, and associated mental disorders. METHOD: A computerized search was performed for articles published in the past decade, and selected papers were highlighted. RESULTS: The study of mental retardation has benefited considerably by advances in medicine generally and by developments in molecular neurobiology in particular. Increasing awareness of psychiatric comorbidity in the context of intellectual disability highlights the need for studies of the phenomenology and treatment of mental disorders in this population. CONCLUSIONS: Although the study of developmental disorders has advanced significantly over the past decade, considerable work remains. Mental retardation is a model for the utility of the biopsychosocial approach in medicine.
Assuntos
Deficiência Intelectual/reabilitação , Adolescente , Animais , Encéfalo/patologia , Criança , Terapia Combinada , Diagnóstico por Imagem , Modelos Animais de Doenças , Síndrome de Down/etiologia , Síndrome de Down/psicologia , Síndrome de Down/reabilitação , Síndrome do Cromossomo X Frágil/etiologia , Síndrome do Cromossomo X Frágil/psicologia , Síndrome do Cromossomo X Frágil/reabilitação , Humanos , Deficiência Intelectual/etiologia , Deficiência Intelectual/psicologia , Escalas de Graduação PsiquiátricaRESUMO
OBJECTIVE: To compare obsessive-compulsive (OC) symptoms in patients with Prader-Willi syndrome (PWS) and symptoms in a group of patients presenting with "Prader-Willi-like" features but without the genetic abnormalities associated with PWS. METHOD: 16 patients aged 4 through 20 years were evaluated in a clinic specializing in the assessment and management of behavioral and food-related problems in PWS. Eight patients were found to have key features of the syndrome but did not have a PWS genotype. These PWS-like subjects were matched to 8 clinic patients with a confirmed deletion of the PWS critical region of the paternally derived chromosome 15. All subjects were evaluated for obesity, IQ, food-related problems, maladaptive behaviors, and non-food-related OC symptoms. RESULTS: There were no differences between the 2 groups with respect to measures of obesity, IQ, food-related difficulties, or overall maladaptive behaviors. The PWS group showed significantly greater numbers of OC symptoms and greater symptom severity. CONCLUSIONS: Patients with PWS have elevated numbers of OC symptoms and significant symptom-related impairment which are not explained by developmental delay, food-related difficulties, or obesity. OC symptoms are part of a behavioral phenotype that accompanies deletions on the proximal long arm of chromosome 15 in PWS.
Assuntos
Transtorno Obsessivo-Compulsivo/diagnóstico , Síndrome de Prader-Willi/diagnóstico , Adolescente , Adulto , Criança , Transtornos do Comportamento Infantil/diagnóstico , Transtornos do Comportamento Infantil/genética , Transtornos do Comportamento Infantil/psicologia , Pré-Escolar , Deleção Cromossômica , Cromossomos Humanos Par 15 , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Transtorno Obsessivo-Compulsivo/genética , Transtorno Obsessivo-Compulsivo/psicologia , Fenótipo , Síndrome de Prader-Willi/genética , Síndrome de Prader-Willi/psicologiaRESUMO
The past two decades of research have demonstrated that Tourette's syndrome (TS) is likely to be more genetically heterogeneous than initially appreciated. Nonetheless, important progress toward the understanding of genetic influences in TS has been made by the combination of family and twin studies, segregation analyses, parametric and nonparametric linkage analyses, and association studies. The identification of genetic factors involved in TS will have important implications for clinical research. Once it is possible to stratify patients meaningfully with respect to known genetic markers, a reassessment of diagnostic nosology, neuroimaging findings, psychopharmacology, and disease course will be possible. Another result of gene identification will be the rapid clarification of additional environmental factors influencing the development of the disorder. Because it may be easier to influence the environment and behavior rather than to change genes, exploration of such gene-environment interactions may lead to the most significant clinical contributions in the near term.
Assuntos
Síndrome de Tourette/genética , Adolescente , Criança , Aberrações Cromossômicas/genética , Transtornos Cromossômicos , Doenças em Gêmeos/genética , Feminino , Ligação Genética/genética , Marcadores Genéticos/genética , Predisposição Genética para Doença/genética , Humanos , Masculino , Meio Social , Síndrome de Tourette/diagnóstico , Estudos em Gêmeos como AssuntoRESUMO
Compared with the general population, individuals with mental retardation demonstrate more susceptibility to psychiatric illness and may display disruptive behaviors. These symptoms significantly can affect an already compromised ability to function and the patient may benefit from pharmacologic intervention. Clinical characteristics of individuals with mental retardation warrant special consideration regarding diagnosis and treatment of their psychiatric and behavioral problems. This article describes the nature of symptoms that are typically the target of pharmacologic intervention, outlines special diagnostic considerations, and examines recent findings and experience with psychotropic medication in mental retardation.