RESUMO
BACKGROUND: Oxytocin (OXT) and prolactin (PRL) are neuropeptide hormones that interact with the serotonin system and are involved in the stress response and social affiliation. In human studies, serum OXT and PRL levels have been associated with depression and related phenotypes. Our purpose was to determine if single nucleotide polymorphisms (SNPs) at the loci for OXT, PRL and their receptors, OXTR and PRLR, were associated with childhood-onset mood disorders (COMD). METHODS: Using 678 families in a family-based association design, we genotyped 16 SNPs at OXT, PRL, OXTR and PRLR to test for association with COMD. RESULTS: No significant associations were found for SNPs in the OXTR, PRL, or PRLR genes. Two of three SNPs 3' of the OXT gene were associated with COMD (p≤0.02), significant after spectral decomposition, but were not significant after additionally correcting for the number of genes tested. Supplementary analyses of parent-of-origin and proband sex effects for OXT SNPs by Fisher's Exact test were not significant after Bonferroni correction. CONCLUSIONS: We have examined 16 OXT and PRL system gene variants, with no evidence of statistically significant association after correction for multiple tests.
Assuntos
Transtornos do Humor/genética , Ocitocina/genética , Polimorfismo de Nucleotídeo Único , Prolactina/genética , Adolescente , Idade de Início , Criança , Família , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Transtornos do Humor/epidemiologia , Receptores de Ocitocina/genética , Receptores da Prolactina/genéticaRESUMO
The chromosome 13q region has been linked to bipolar disorder in a number of genome scans as well as focused linkage studies. Previously we identified linkage to the 13q32 region in a genome scan of 146 affected sibling pair families from Hungary with juvenile-onset mood disorders. Within this region are the overlapping genes G72/G30, with G72 now officially named as D-amino-acid oxidase activator (DAOA). This locus has been associated with panic disorder, schizophrenia, and bipolar disorder. In this study, we tested for association to 11 markers in these genes and mood disorders in a sample of 646 nuclear families identified with a proband with onset of a mood disorder before 14.9 years of age. We identified evidence for association to three markers within the gene (rs2391191, rs3918341, rs1935062), two of which had been associated with bipolar disorder in previous studies. When corrected for the number of markers tested, the results were no longer significant, however the prior evidence for association of this gene in multiple studies points to this gene as a potential contributor to juvenile-onset mood disorders.
Assuntos
D-Aminoácido Oxidase/genética , Transtornos do Humor/enzimologia , Transtornos do Humor/genética , Adolescente , Idade de Início , Criança , Regulação da Expressão Gênica , Frequência do Gene/genética , Predisposição Genética para Doença , Humanos , Hungria/epidemiologia , Desequilíbrio de Ligação/genética , Metanálise como Assunto , Transtornos do Humor/epidemiologia , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
OBJECTIVE: To examine various forms of suicidality specified in DSM-IV and their clinical characteristics in a large sample of children and adolescents with major depressive disorder (MDD). METHOD: Subjects included 553 children and adolescents (aged 7.0-14.9 years) recruited between April 2000 and December 2004 from 23 mental health facilities in Hungary. Subjects received standardized clinical evaluations and best-estimate consensus DSM-IV diagnoses of MDD. All subjects were in a current episode of MDD at their assessment date. RESULTS: Approximately 68% of the sample had recurrent thoughts of death, 48% had suicidal ideation, 30% had suicide plan, and 12% had attempted suicide. Compared with nonsuicidal peers, suicidal children and adolescents were more severely depressed, had more depressive symptoms, and more likely had comorbid disorders. However, depressed children and adolescents with various forms of suicidality were very similar in clinical characteristics. Feelings of worthlessness, depressed mood, psychomotor agitation, and comorbid separation anxiety and conduct disorders were independent correlates of at least 1 form of suicidality. Only feelings of worthlessness was related to all 4 suicidal behaviors, after adjustment for other depressive symptoms, comorbid disorders, and demographics. CONCLUSION: Clinical characteristics differ between nonsuicidal and suicidal children and adolescents but are very similar across various forms of suicidality. Feelings of worthlessness may play a central role in the development of suicidal behavior. Interventions toward the enhancement of self-esteem and amelioration of underlying psychopathology may be crucial for the prevention of suicide attempts in depressed children and adolescents.
