RESUMEN
Obsessive-compulsive disorder (OCD) and Autism spectrum disorder (ASD) are both highly heritable neurodevelopmental disorders that conceivably share genetic risk factors. However, the underlying genetic determinants remain largely unknown. In this work, the authors describe a combined genome-wide association study (GWAS) of ASD and OCD. The OCD dataset includes 2998 individuals in nuclear families. The ASD dataset includes 6898 individuals in case-parents trios. GWAS summary statistics were examined for potential enrichment of functional variants associated with gene expression levels in brain regions. The top ranked SNP is rs4785741 (chromosome 16) with P value=6.9×10-7 in our re-analysis. Polygenic risk score analyses were conducted to investigate the genetic relationship within and across the two disorders. These analyses identified a significant polygenic component of ASD, predicting 0.11% of the phenotypic variance in an independent OCD data set. In addition, we examined the genomic architecture of ASD and OCD by estimating heritability on different chromosomes and different allele frequencies, analyzing genome-wide common variant data by using the Genome-wide Complex Trait Analysis (GCTA) program. The estimated global heritability of OCD is 0.427 (se=0.093) and 0.174 (se=0.053) for ASD in these imputed data.
Asunto(s)
Trastorno del Espectro Autista/genética , Estudio de Asociación del Genoma Completo/métodos , Herencia Multifactorial/genética , Trastorno Obsesivo Compulsivo/genética , Polimorfismo de Nucleótido Simple/genética , Carácter Cuantitativo Heredable , Trastorno del Espectro Autista/diagnóstico , Bases de Datos Genéticas/estadística & datos numéricos , Humanos , Trastorno Obsesivo Compulsivo/diagnóstico , Factores de RiesgoRESUMEN
Up to 30% of patients with obsessive-compulsive disorder (OCD) exhibit an inadequate response to serotonin reuptake inhibitors (SRIs). To date, genetic predictors of OCD treatment response have not been systematically investigated using genome-wide association study (GWAS). To identify specific genetic variations potentially influencing SRI response, we conducted a GWAS study in 804 OCD patients with information on SRI response. SRI response was classified as 'response' (n=514) or 'non-response' (n=290), based on self-report. We used the more powerful Quasi-Likelihood Score Test (the MQLS test) to conduct a genome-wide association test correcting for relatedness, and then used an adjusted logistic model to evaluate the effect size of the variants in probands. The top single-nucleotide polymorphism (SNP) was rs17162912 (P=1.76 × 10(-8)), which is near the DISP1 gene on 1q41-q42, a microdeletion region implicated in neurological development. The other six SNPs showing suggestive evidence of association (P<10(-5)) were rs9303380, rs12437601, rs16988159, rs7676822, rs1911877 and rs723815. Among them, two SNPs in strong linkage disequilibrium, rs7676822 and rs1911877, located near the PCDH10 gene, gave P-values of 2.86 × 10(-6) and 8.41 × 10(-6), respectively. The other 35 variations with signals of potential significance (P<10(-4)) involve multiple genes expressed in the brain, including GRIN2B, PCDH10 and GPC6. Our enrichment analysis indicated suggestive roles of genes in the glutamatergic neurotransmission system (false discovery rate (FDR)=0.0097) and the serotonergic system (FDR=0.0213). Although the results presented may provide new insights into genetic mechanisms underlying treatment response in OCD, studies with larger sample sizes and detailed information on drug dosage and treatment duration are needed.
Asunto(s)
Trastorno Obsesivo Compulsivo/genética , Adolescente , Adulto , Anciano , Niño , Femenino , Predisposición Genética a la Enfermedad , Variación Genética , Estudio de Asociación del Genoma Completo , Humanos , Desequilibrio de Ligamiento , Masculino , Proteínas de la Membrana/genética , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Autoinforme , Inhibidores Selectivos de la Recaptación de Serotonina/metabolismo , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: The purpose of this study was to investigate whether dependent personality and/or general personality dimensions might explain the strong relationships between separation anxiety disorder (Sep-AD) and three other anxiety disorders (agoraphobia, panic disorder and social anxiety disorder) in individuals with obsessive compulsive disorder (OCD). METHODS: Using data from 509 adult participants collected during the OCD Collaborative Genetic Study, we used logistic regression models to evaluate the relationships between Sep-AD, dependent personality score, general personality dimensions and three additional anxiety disorders. RESULTS: The dependent personality score was strongly associated with Sep-AD and the other anxiety disorders in models adjusted for age at interview, age at onset of OC symptoms and worst ever OCD severity score. Several general personality dimensions, especially neuroticism, extraversion and conscientiousness, were also related to Sep-AD and the other anxiety disorders. Sep-AD was not independently related to these anxiety disorders, in multivariate models including general personality and dependent personality disorder scores. CONCLUSIONS: The results suggest that Sep-AD in childhood and these other anxiety disorders in adulthood are consequences of dependent personality disorder (for agoraphobia and panic disorder) or introversion (for social phobia). It is unknown whether these results would be similar in a non-OCD sample.
Asunto(s)
Agorafobia/psicología , Ansiedad de Separación/psicología , Trastorno de Personalidad Dependiente/psicología , Trastorno Obsesivo Compulsivo/psicología , Trastorno de Pánico/psicología , Conducta Social , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Trastornos de Ansiedad/psicología , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Trastornos de la Personalidad/psicología , Adulto JovenRESUMEN
Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by intrusive thoughts and urges and repetitive, intentional behaviors that cause significant distress and impair functioning. The OCD Collaborative Genetics Association Study (OCGAS) is comprised of comprehensively assessed OCD patients with an early age of OCD onset. After application of a stringent quality control protocol, a total of 1065 families (containing 1406 patients with OCD), combined with population-based samples (resulting in a total sample of 5061 individuals), were studied. An integrative analyses pipeline was utilized, involving association testing at single-nucleotide polymorphism (SNP) and gene levels (via a hybrid approach that allowed for combined analyses of the family- and population-based data). The smallest P-value was observed for a marker on chromosome 9 (near PTPRD, P=4.13 × 10(-)(7)). Pre-synaptic PTPRD promotes the differentiation of glutamatergic synapses and interacts with SLITRK3. Together, both proteins selectively regulate the development of inhibitory GABAergic synapses. Although no SNPs were identified as associated with OCD at genome-wide significance level, follow-up analyses of genome-wide association study (GWAS) signals from a previously published OCD study identified significant enrichment (P=0.0176). Secondary analyses of high-confidence interaction partners of DLGAP1 and GRIK2 (both showing evidence for association in our follow-up and the original GWAS study) revealed a trend of association (P=0.075) for a set of genes such as NEUROD6, SV2A, GRIA4, SLC1A2 and PTPRD. Analyses at the gene level revealed association of IQCK and C16orf88 (both P<1 × 10(-)(6), experiment-wide significant), as well as OFCC1 (P=6.29 × 10(-)(5)). The suggestive findings in this study await replication in larger samples.
Asunto(s)
Salud de la Familia , Predisposición Genética a la Enfermedad/genética , Trastorno Obsesivo Compulsivo/genética , Adulto , Cromosomas Humanos Par 9/genética , Conducta Cooperativa , Femenino , Estudios de Seguimiento , Perfilación de la Expresión Génica , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Polimorfismo de Nucleótido Simple , Proteínas Tirosina Fosfatasas Clase 2 Similares a Receptores/genética , Adulto JovenRESUMEN
The neuronal glutamate transporter gene SLC1A1 is a candidate gene for obsessive-compulsive disorder (OCD) based on linkage studies and convergent evidence implicating glutamate in OCD etiology. The 3' end of SLC1A1 is the only genomic region with consistently demonstrated OCD association, especially when analyzing male-only probands. However, specific allele associations have not been consistently replicated, and recent OCD genome-wide association and meta-analysis studies have not incorporated all previously associated SLC1A1 SNPs. To clarify the nature of association between SLC1A1 and OCD, pooled analysis was performed on all available relevant raw study data, comprising a final sample of 815 trios, 306 cases and 634 controls. This revealed weak association between OCD and one of nine tested SLC1A1 polymorphisms (rs301443; uncorrected P = 0.046; non-significant corrected P). Secondary analyses of male-affecteds only (N = 358 trios and 133 cases) demonstrated modest association between OCD and a different SNP (rs12682807; uncorrected P = 0.012; non-significant corrected P). Findings of this meta-analysis are consistent with the trend of previous candidate gene studies in psychiatry and do not clarify the putative role of SLC1A1 in OCD pathophysiology. Nonetheless, it may be important to further examine the potential associations demonstrated in this amalgamated sample, especially since the SNPs with modest associations were not included in the more highly powered recent GWAS or in a past meta-analysis including five SLC1A1 polymorphisms. This study underscores the need for much larger sample sizes in future genetic association studies and suggests that next-generation sequencing may be beneficial in examining the potential role of rare variants in OCD.
Asunto(s)
Sistema de Transporte de Aminoácidos X-AG/genética , Neuronas/metabolismo , Trastorno Obsesivo Compulsivo/genética , Sistema de Transporte de Aminoácidos X-AG/química , Estudios de Casos y Controles , Femenino , Marcadores Genéticos , Humanos , Masculino , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: Experts have proposed removing obsessive-compulsive disorder (OCD) from the anxiety disorders section and grouping it with putatively related conditions in DSM-5. The current study uses co-morbidity and familiality data to inform these issues. METHOD: Case family data from the OCD Collaborative Genetics Study (382 OCD-affected probands and 974 of their first-degree relatives) were compared with control family data from the Johns Hopkins OCD Family Study (73 non-OCD-affected probands and 233 of their first-degree relatives). RESULTS: Anxiety disorders (especially agoraphobia and generalized anxiety disorder), cluster C personality disorders (especially obsessive-compulsive and avoidant), tic disorders, somatoform disorders (hypochondriasis and body dysmorphic disorder), grooming disorders (especially trichotillomania and pathological skin picking) and mood disorders (especially unipolar depressive disorders) were more common in case than control probands; however, the prevalences of eating disorders (anorexia and bulimia nervosa), other impulse-control disorders (pathological gambling, pyromania, kleptomania) and substance dependence (alcohol or drug) did not differ between the groups. The same general pattern was evident in relatives of case versus control probands. Results in relatives did not differ markedly when adjusted for demographic variables and proband diagnosis of the same disorder, though the strength of associations was lower when adjusted for OCD in relatives. Nevertheless, several anxiety, depressive and putative OCD-related conditions remained significantly more common in case than control relatives when adjusting for all of these variables simultaneously. CONCLUSIONS: On the basis of co-morbidity and familiality, OCD appears related both to anxiety disorders and to some conditions currently classified in other sections of DSM-IV.
Asunto(s)
Trastornos de Ansiedad/epidemiología , Familia/psicología , Predisposición Genética a la Enfermedad , Trastornos Mentales/epidemiología , Adolescente , Adulto , Trastornos de Ansiedad/clasificación , Trastornos de Ansiedad/genética , Trastornos de Ansiedad/patología , Niño , Preescolar , Comorbilidad , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Métodos Epidemiológicos , Femenino , Humanos , Entrevista Psicológica , Masculino , Trastornos Mentales/clasificación , Trastornos Mentales/genética , Persona de Mediana Edad , Trastorno Obsesivo Compulsivo/clasificación , Trastorno Obsesivo Compulsivo/epidemiología , Trastorno Obsesivo Compulsivo/genética , Trastorno Obsesivo Compulsivo/patología , Fenotipo , Factores Socioeconómicos , Adulto JovenRESUMEN
BACKGROUND: Despite evidence that obsessive-compulsive disorder (OCD) is a familial neuropsychiatric condition, progress aimed at identifying genetic determinants of the disorder has been slow. The OCD Collaborative Genetics Study (OCGS) has identified several OCD susceptibility loci through linkage analysis. METHODS: In this study we investigate two regions on chromosomes 15q and 1q by first refining the linkage region using additional short tandem repeat polymorphic (STRP) markers. We then performed association analysis on single nucleotide polymorphisms (SNP) genotyped (markers placed every 2-4 kb) in the linkage regions in the OCGS sample of 376 rigorously phenotyped affected families. RESULTS: Three SNPs are most strongly associated with OCD: rs11854486 (P = 0.00005 [0.046 after adjustment for multiple tests]; genetic relative risk (GRR) = 11.1 homozygous and 1.6 heterozygous) and rs4625687 [P = 0.00007 (after adjustment = 0.06); GRR = 2.4] on 15q; and rs4387163 (P = 0.0002 (after adjustment = 0.08); GRR = 1.97) on 1q. The first SNP is adjacent to NANOGP8, the second SNP is in MEIS2, and the third is 150 kb between PBX1 and LMX1A. CONCLUSIONS: All the genes implicated by association signals are homeobox genes and are intimately involved in neurodevelopment. PBX1 and MEIS2 exert their effects by the formation of a heterodimeric complex, which is involved in development of the striatum, a brain region involved in the pathophysiology of OCD. NANOGP8 is a retrogene of NANOG, a homeobox transcription factor known to be involved in regulation of neuronal development. These findings need replication; but support the hypothesis that genes involved in striatal development are implicated in the pathogenesis of OCD.
Asunto(s)
Genes Homeobox/genética , Predisposición Genética a la Enfermedad , Trastorno Obsesivo Compulsivo/genética , Cromosomas Humanos Par 1/genética , Cromosomas Humanos Par 15/genética , Ligamiento Genético , Marcadores Genéticos , Estudio de Asociación del Genoma Completo , Humanos , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
Genetic association studies of SLC6A4 (SERT) and obsessive-compulsive disorder (OCD) have been equivocal. We genotyped 1241 individuals in 278 pedigrees from the OCD Collaborative Genetics Study for 13 single-nucleotide polymorphisms, for the linked polymorphic region (LPR) indel with molecular haplotypes at rs25531, for VNTR polymorphisms in introns 2 and 7 and for a 381-bp deletion 3' to the LPR. We analyzed using the Family-Based Association Test (FBAT) under additive, dominant, recessive and genotypic models, using both OCD and sex-stratified OCD as phenotypes. Two-point FBAT analysis detected association between Int2 (P = 0.0089) and Int7 (P = 0.0187) (genotypic model). Sex-stratified two-point analysis showed strong association in females with Int2 (P<0.0002), significant after correction for linkage disequilibrium, and multiple marker and model testing (P(Adj) = 0.0069). The SLC6A4 gene is composed of two haplotype blocks (our data and the HapMap); FBAT whole-marker analysis conducted using this structure was not significant. Several noteworthy nonsignificant results have emerged. Unlike Hu et al., we found no evidence for overtransmission of the LPR L(A) allele (genotype relative risk = 1.11, 95% confidence interval: 0.77-1.60); however, rare individual haplotypes containing L(A) with P<0.05 were observed. Similarly, three individuals (two with OCD/OCPD) carried the rare I425V SLC6A4 variant, but none of them passed it on to their six OCD-affected offspring, suggesting that it is unlikely to be solely responsible for the 'OCD plus syndrome', as reported by Ozaki et al. In conclusion, we found evidence of genetic association at the SLC6A4 locus with OCD. A noteworthy lack of association at the LPR, LPR-rs25531 and rare 425V variants suggests that hypotheses about OCD risk need revision to accommodate these new findings, including a possible gender effect.
Asunto(s)
Trastorno Obsesivo Compulsivo/genética , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genética , Adolescente , Adulto , Niño , Femenino , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Masculino , Linaje , Polimorfismo de Nucleótido Simple , Distribución por Sexo , Estados Unidos , Adulto JovenRESUMEN
SLC1A encodes the neuronal and epithelial glutamate transporter and was previously tested as a candidate for obsessive-compulsive disorder (OCD) by several research groups. Recently, three independent research groups reported significant association findings between OCD and several genetic variants in SLC1A1. This study reports the results from a family-based association study, which examined the association between 13 single nucleotide polymorphisms (SNPs) within or in proximity to the SLC1A1 gene. Although we did not replicate association findings for those significant SNPs reported by previous studies, our study indicated a strong association signal with the SNP RS301443 (P-value = 0.000067; Bonferroni corrected P-value = 0.0167) under a dominant model, with an estimated odds ratio of 3.5 (confidence interval: 2.66-4.50). Further, we conducted single SNP analysis after stratifying the full data set by the gender status of affected in each family. The P-value for RS301443 in families with the male affected was 0.00027, and the P-value in families with female affected was 0.076. The fact that we identified a signal which was not previously reported by the other research groups may be due to differences in study designs and sample ascertainment. However, it is also possible that this significant SNP may be part of a regulator for SLC1A1, given that it is roughly 7.5 kb away from the boundary of the SLC1A1 gene. However, this potential finding needs to be validated biologically. Further functional studies in this region are planned by this research group.
Asunto(s)
Transportador 3 de Aminoácidos Excitadores/genética , Familia , Predisposición Genética a la Enfermedad , Trastorno Obsesivo Compulsivo/genética , Adolescente , Edad de Inicio , Niño , Femenino , Genotipo , Humanos , Masculino , Núcleo Familiar , Linaje , Polimorfismo de Nucleótido Simple , Adulto JovenRESUMEN
BACKGROUND: Obsessive-compulsive disorder (OCD) is probably an etiologically heterogeneous condition. Many patients manifest other psychiatric syndromes. This study investigated the relationship between OCD and co-morbid conditions to identify subtypes. METHOD: Seven hundred and six individuals with OCD were assessed in the OCD Collaborative Genetics Study (OCGS). Multi-level latent class analysis was conducted based on the presence of eight co-morbid psychiatric conditions [generalized anxiety disorder (GAD), major depression, panic disorder (PD), separation anxiety disorder (SAD), tics, mania, somatization disorders (Som) and grooming disorders (GrD)]. The relationship of the derived classes to specific clinical characteristics was investigated. RESULTS: Two and three classes of OCD syndromes emerge from the analyses. The two-class solution describes lesser and greater co-morbidity classes and the more descriptive three-class solution is characterized by: (1) an OCD simplex class, in which major depressive disorder (MDD) is the most frequent additional disorder; (2) an OCD co-morbid tic-related class, in which tics are prominent and affective syndromes are considerably rarer; and (3) an OCD co-morbid affective-related class in which PD and affective syndromes are highly represented. The OCD co-morbid tic-related class is predominantly male and characterized by high conscientiousness. The OCD co-morbid affective-related class is predominantly female, has a young age at onset, obsessive-compulsive personality disorder (OCPD) features, high scores on the 'taboo' factor of OCD symptoms, and low conscientiousness. CONCLUSIONS: OCD can be classified into three classes based on co-morbidity. Membership within a class is differentially associated with other clinical characteristics. These classes, if replicated, should have important implications for research and clinical endeavors.
Asunto(s)
Trastornos Mentales/clasificación , Trastorno Obsesivo Compulsivo/clasificación , Adulto , Factores de Edad , Edad de Inicio , Comorbilidad , Estudios Transversales , Trastorno Depresivo Mayor/clasificación , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/genética , Trastorno Depresivo Mayor/psicología , Femenino , Predisposición Genética a la Enfermedad/genética , Humanos , Masculino , Trastornos Mentales/diagnóstico , Trastornos Mentales/genética , Trastornos Mentales/psicología , Trastorno Obsesivo Compulsivo/diagnóstico , Trastorno Obsesivo Compulsivo/genética , Trastorno Obsesivo Compulsivo/psicología , Determinación de la Personalidad/estadística & datos numéricos , Trastornos de la Personalidad/clasificación , Trastornos de la Personalidad/diagnóstico , Trastornos de la Personalidad/genética , Trastornos de la Personalidad/psicología , Psicometría , Factores Sexuales , Trastornos de Tic/clasificación , Trastornos de Tic/diagnóstico , Trastornos de Tic/genética , Trastornos de Tic/psicologíaRESUMEN
Obsessive-compulsive disorder (OCD) is the tenth most disabling medical condition worldwide. Twin and family studies implicate a genetic etiology for this disorder, although specific genes have yet to be identified. Here, we present the first large-scale model-free linkage analysis of both extended and nuclear families using both 'broad' (definite and probable diagnoses) and 'narrow' (definite only) definitions of OCD. We conducted a genome-scan analysis of 219 families collected as part of the OCD Collaborative Genetics Study. Suggestive linkage signals were revealed by multipoint analysis on chromosomes 3q27-28 (P=0.0003), 6q (P=0.003), 7p (P=0.001), 1q (P=0.003), and 15q (P=0.006). Using the 'broad' OCD definition, we observed the strongest evidence for linkage on chromosome 3q27-28. The maximum overall Kong and Cox LODall score (2.67) occurred at D3S1262 and D3S2398, and simulation based P-values for these two signals were 0.0003 and 0.0004, respectively, although for both signals, the simulation-based genome-wide significance levels were 0.055. Covariate-linkage analyses implicated a possible role of gene(s) on chromosome 1 in increasing the risk for an earlier onset form of OCD. We are currently pursuing fine mapping in the five regions giving suggestive signals, with a particular focus on 3q27-28. Given probable etiologic heterogeneity in OCD, mapping gene(s) involved in the disorder may be enhanced by replication studies, large-scale family-based linkage studies, and the application of novel statistical methods.
Asunto(s)
Cromosomas Humanos , Genoma Humano , Genómica , Trastorno Obsesivo Compulsivo/genética , Cromosomas Humanos Par 1 , Cromosomas Humanos Par 15 , Cromosomas Humanos Par 3 , Cromosomas Humanos Par 6 , Cromosomas Humanos Par 7 , Salud de la Familia , Predisposición Genética a la Enfermedad , Humanos , Escala de Lod , FenotipoRESUMEN
Hoarding occurs relatively frequently in obsessive-compulsive disorder (OCD), and there is evidence that patients with hoarding symptoms have more severe OCD and are less responsive to treatment. In the present study, we investigated hoarding symptoms in 126 subjects with OCD. Nearly 30% of the subjects had hoarding symptoms; hoarding was twice as prevalent in males than females. Compared to the 90 non-hoarding subjects, the 36 hoarding individuals had an earlier age at onset of, and more severe, obsessive-compulsive symptoms. Hoarders had greater prevalences of symmetry obsessions, counting compulsions, and ordering compulsions. Hoarders also had greater prevalences of social phobia, personality disorders, and pathological grooming behaviors (skin picking, nail biting, and trichotillomania). Hoarding and tics were more frequent in first-degree relatives of hoarding than non-hoarding probands. The findings suggest that the treatment of OCD patients with hoarding symptoms may be complicated by more severe OCD and the presence of co-occurring disorders. Hoarding appears to be transmitted in some OCD families and may differentiate a clinical subgroup of OCD.
Asunto(s)
Trastornos de Alimentación y de la Ingestión de Alimentos/epidemiología , Trastorno Obsesivo Compulsivo/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Comorbilidad , Trastornos de Alimentación y de la Ingestión de Alimentos/diagnóstico , Trastornos de Alimentación y de la Ingestión de Alimentos/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastorno Obsesivo Compulsivo/diagnóstico , Trastorno Obsesivo Compulsivo/terapia , Trastornos de la Personalidad/diagnóstico , Trastornos de la Personalidad/epidemiología , Prevalencia , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Obsessive-compulsive disorder (OCD) and tic disorders have phenomenological and familial-genetic overlaps. An OCD family study sample that excludes Tourette's syndrome in probands is used to examine whether tic disorders are part of the familial phenotype of OCD. METHODS: Eighty case and 73 control probands and their first-degree relatives were examined by experienced clinicians using the Schedule for Affective Disorders and Schizophrenia-Lifetime Anxiety version. DSM-IV psychiatric diagnoses were ascertained by a best-estimate consensus procedure. The prevalence and severity of tic disorders, age-at-onset of OCD symptoms, and transmission of OCD and tic disorders by characteristics and type of proband (OCD + tic disorder, OCD - tic disorder) were examined in relatives. RESULTS: Case probands and case relatives had a greater lifetime prevalence of tic disorders compared to control subjects. Tic disorders spanning a wide severity range were seen in case relatives; only mild severity was seen in control relatives. Younger age-at-onset of OCD symptoms and possibly male gender in case probands were associated with increased tic disorders in relatives. Although relatives of OCD + tic disorder and OCD - tic disorder probands had similar prevalences of tic disorders, this result is not conclusive. CONCLUSIONS: Tic disorders constitute an alternate expression of the familial OCD phenotype.
Asunto(s)
Trastorno Obsesivo Compulsivo/genética , Fenotipo , Trastornos de Tic/genética , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Frecuencia de los Genes/genética , Predisposición Genética a la Enfermedad/genética , Humanos , Masculino , Trastorno Obsesivo Compulsivo/diagnóstico , Trastornos de Tic/diagnóstico , Síndrome de Tourette/diagnóstico , Síndrome de Tourette/genéticaRESUMEN
OBJECTIVE: To examine psychostimulant response in preschool children with attention-deficit/hyperactivity disorder (ADHD) in an outpatient child psychiatry clinic (housed within a developmental disorders institution) over 3, 12, and 24 months of treatment. METHOD: A systematic retrospective chart review was conducted for 27 preschool children with ADHD who were started on psychostimulants between the ages of 3 and 5 years, inclusive. Two child and adolescent psychiatrists reviewed each chart independently, using the Clinical Global Impressions (CGI) scale to rate the severity of illness and global improvement and the Side Effects Rating Form to rate side effects. RESULTS: Over 24 months, psychostimulants were stopped in three children (11%) because of side effects and concomitant psychotropic medications were added in seven children (26%). The CGI severity-of-illness ratings showed a significant effect of time over 3, 12, and 24 months of psychostimulant treatment (all p values < .0001). Rate of response was 74% at 3 months and 70% at 12 and 24 months. Side effects were mostly mild and occurred in 63% of the children at 3 months, 41% at 12 months, and 29% at 24 months. CONCLUSIONS: The findings suggest that preschool children with developmental disorders respond to psychostimulants but need close monitoring because of frequent side effects. Inasmuch as the study participants were recruited from a child psychiatry clinic housed within a developmental disorders institution and had a high rate of developmental disorders, the findings may not generalize to other preschool children with ADHD.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Estimulantes del Sistema Nervioso Central/uso terapéutico , Discapacidades del Desarrollo/complicaciones , Metilfenidato/uso terapéutico , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Preescolar , Femenino , Humanos , Masculino , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
OBJECTIVE: This study investigates the relationship of specific anxiety and affective disorders to obsessive-compulsive disorder (OCD) in a blind, controlled family study. METHOD: Eighty case and 73 control probands, as well as 343 case and 300 control first-degree relatives of these probands, participated in the study. Subjects were examined by psychologists or psychiatrists using the Schedule for Affective Disorder and Schizophrenia-Lifetime Anxiety version (SADS-LA). Two experienced psychiatrists independently reviewed all clinical materials, and final diagnoses were made according to DSM-IV criteria, by consensus procedure. RESULTS: Except for bipolar disorder, all anxiety and affective disorders investigated were more frequent in case than control probands. Substance dependence disorders were not more frequent. Generalized anxiety disorder (GAD), panic disorder, agoraphobia, separation anxiety disorder (SAD) and recurrent major depression were more common in case than control relatives. These disorders occurred more frequently if the relative was diagnosed with OCD. Only GAD and agoraphobia were more frequent in case relatives independent of OCD. CONCLUSION: GAD and agoraphobia share a common familial aetiology with OCD. The other anxiety and affective disorders, when comorbid with OCD, may emerge as a consequence of the OCD or as a more complex syndrome.
Asunto(s)
Trastornos de Ansiedad/diagnóstico , Trastornos del Humor/diagnóstico , Trastorno Obsesivo Compulsivo/diagnóstico , Adolescente , Adulto , Trastornos de Ansiedad/epidemiología , Trastornos de Ansiedad/genética , Niño , Comorbilidad , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo Mayor/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos del Humor/epidemiología , Trastornos del Humor/genética , Trastorno Obsesivo Compulsivo/epidemiología , Trastorno Obsesivo Compulsivo/genética , Prevalencia , Escalas de Valoración Psiquiátrica , Recurrencia , Método Simple CiegoRESUMEN
Discusses pharmacological treatment of childhood obsessive-compulsive disorder (OCD), chronic and underrecognized psychiatric condition that affects up to 2% to 3% of children and adolescents. Research in OCD in children, including neuropharmacology, brain imaging, genetics, and clinical phenomenology, informs current views of OCD pathophysiology. Contemporary research supports the notion of a dysregulation in serotonin subsystems in the central nervous system, with target areas of dysfunction including basal ganglia and orbitofrontal cortex. Pharmacotherapy, along with cognitive-behavioral approaches, constitutes the indicated treatment for childhood OCD. Pharmacological treatment is best guided by a phenomenological understanding of the type of obsessions and compulsions, the intensity and frequency of their presentation with attention to behavioral reinforcements, and psychosocial factors that affect the course of the disease. Serotonin-enhancing agents, such as fluoxetine, fluvoxamine, paroxetine, and sertraline and citalopram (SSRIs) are first-line pharmacological agents, whereas refractory symptoms can be treated by augmentation with neuroleptics or other agents. Clomipramine is as effective as the SSRIs but its use may be accompanied by increased side effects. Genetic factors probably influence susceptibility to OCD as well as response to treatment, and the elucidation of these and other risk factors will be important elements in the future understanding and treatment of this disorder.
Asunto(s)
Trastorno Obsesivo Compulsivo/tratamiento farmacológico , Trastorno Obsesivo Compulsivo/psicología , Teoría Psicológica , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Antipsicóticos/uso terapéutico , Encéfalo/fisiopatología , Niño , Quimioterapia Combinada , Predisposición Genética a la Enfermedad , Humanos , Neurotransmisores , Trastorno Obsesivo Compulsivo/fisiopatología , Inhibidores Selectivos de la Recaptación de Serotonina/farmacologíaAsunto(s)
Trastornos Disruptivos, del Control de Impulso y de la Conducta/diagnóstico , Trastorno Obsesivo Compulsivo/diagnóstico , Piel/lesiones , Adulto , Edad de Inicio , Niño , Comorbilidad , Diagnóstico Diferencial , Trastornos Disruptivos, del Control de Impulso y de la Conducta/epidemiología , Trastornos Disruptivos, del Control de Impulso y de la Conducta/psicología , Familia , Femenino , Humanos , Masculino , Trastornos Mentales/diagnóstico , Trastornos Mentales/epidemiología , Trastorno Obsesivo Compulsivo/epidemiología , Trastorno Obsesivo Compulsivo/psicología , Prevalencia , Escalas de Valoración Psiquiátrica/estadística & datos numéricosRESUMEN
This paper reviews research in pediatric psychopharmacology over the past decade. The authors first discuss social, economic, and other influences on pediatric psychopharmacology research and prescribing patterns including changing models of childhood psychopathology, increased government funding, and changes in industry regulations. Definitions are offered for current research terminology including efficacy, effectiveness, and adverse events. Design trends and new approaches to outcome measurement are also presented. New data from the last 10 years of research is reviewed for each major class of psychotropic agents. Criteria for inclusion in the review are presented and include aspects of study design (placebo-controlled, large sample size), source of funding (government funded vs. industry), and vision (creative applications). Data for short-term efficacy, long-term efficacy, effectiveness, and safety and adverse events are discussed for each class of medication, although for many, there remains little empirical data. Findings for stimulants, selective serotonin reuptake inhibitors, neuroleptics, alpha-adrenergic agonists, mood stabilizers, buproprion, secretin, naltrexone, immune therapies, and natural supplements are all presented. Finally, the authors offer some speculations regarding the future of pediatric psychopharmacology research.