ABSTRACT
The authors summarize their experiences in research organization accumulated during 13 years. At first they outline preliminary studies which are prerequisites of high prestige international grants. Then they describe the huge administrative apparatus dedicated - besides skilled professionals - for the construction and organization of the research, the management, continuous checking and evaluation of data in such a multisite study. Finally, they report on the scientific results obtained after 13 years of hard work.
Subject(s)
Depression/epidemiology , Depression/etiology , Depressive Disorder, Major/epidemiology , Depressive Disorder, Major/etiology , Program Development , Research Design , Adolescent , Child , Depression/complications , Depression/diagnosis , Depression/economics , Depression/genetics , Depressive Disorder, Major/complications , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/economics , Depressive Disorder, Major/genetics , Female , Financing, Government , Humans , Hungary/epidemiology , Male , National Institute of Mental Health (U.S.) , Prevalence , Program Development/economics , Program Development/methods , Program Evaluation , Research Support as Topic , Risk Factors , Suicide/statistics & numerical data , Suicide, Attempted/statistics & numerical data , Surveys and Questionnaires , United StatesABSTRACT
Mood disorders (bipolar and depressive disorders) in children and adolescents are associated with significant morbidity and mortality. Twin and family studies, for the most part, indicate higher familiality and heritability for mood disorders that onset in childhood/adolescence than those that onset in adulthood. To identify the genetic contribution to mood disorders that onset in childhood/adolescence, we performed a genome scan on 146 nuclear families from Hungary containing an affected proband and affected siblings. In total, the pedigrees contained 303 affected children: 146 probands, 137 siblings with a first episode of mood disorder before 14.9 years of age, and 20 siblings with onset of their first episode after 14.9 years of age but before the age of 18. The results of the genome scan using 405 microsatellite markers did not provide evidence for linkage at the recommended genome wide significance level for any novel loci. However, markers on two chromosomes, 13q and Xq, provided evidence for linkage in regions previously identified as linked to bipolar disorder in multiple studies. For the marker on chromosome 13q the peak non-parametric multipoint LOD score was at the marker D13S779 (LOD = 1.5, P = 0.004). On chromosome Xq, evidence for linkage was observed across a large region spanning two regions previously linked to bipolar disorder; Xq24 to Xq28, with a peak at marker TTTA062 (LOD 2.10, P = 0.0009) in Xq28. Results for these regions exceed the recommended P-value for a replication study of P < 0.01 and thus provide evidence for these two loci as contributing to mood disorders with juvenile onset.
Subject(s)
Chromosomes, Human, Pair 13 , Chromosomes, Human, X , Genome-Wide Association Study , Mood Disorders/genetics , Siblings , Adolescent , Age of Onset , Child , Chromosome Mapping , Chromosomes, Human, Pair 13/genetics , Chromosomes, Human, X/genetics , Female , Genetic Linkage , Humans , Male , Matched-Pair Analysis , Mood Disorders/epidemiologyABSTRACT
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.
Subject(s)
D-Amino-Acid Oxidase/genetics , Mood Disorders/enzymology , Mood Disorders/genetics , Adolescent , Age of Onset , Child , Gene Expression Regulation , Gene Frequency/genetics , Genetic Predisposition to Disease , Humans , Hungary/epidemiology , Linkage Disequilibrium/genetics , Meta-Analysis as Topic , Mood Disorders/epidemiology , Polymorphism, Single Nucleotide/geneticsABSTRACT
In this paper, we report the case of a 6(1/2)-year-old male patient diagnosed with attention-deficit/hyperactivity disorder (ADHD) who developed orofacial and extremity dyskinesias immediately after methylphenidate treatment. The episode lasted 5 hours, peaking in intensity 2 hours after the medication was administered before gradually subsiding. Five hours after the methylphenidate was administered, the child became extremely irritated and aggressive, which lasted approximately 2 hours. The patient's general intelligence (IQ) was measured to be below the normal range. The potential relationship between methylphenidate intake and the development of dyskinesia calls into question different mechanisms involving drug-receptor interaction or individual drug sensitivity related to a lower IQ. Our case report has practical implications for physicians by raising their awareness of dyskinesia as a potential side effect of methylphenidate treatment.