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Biomedical subjects

I Waldman

Publications and source records attributed to I Waldman.

At least 19 recordsLinked to original sources
PubMed2004

Linkage of the dopamine receptor D1 gene to attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) has a strong genetic basis, and evidence from human and animal studies suggests the dopamine receptor D1 gene, DRD1, to be a good candidate for involvement. Here, we tested for linkage of DRD1 to ADHD by examining the inheritance of four biallelic DRD1 polymorphisms [D1P.5 (-1251HaeIII), D1P.6 (-800HaeIII), D1.1 (-48DdeI) and D1.7 (+1403Bsp1286I)] in a sample of 156 ADHD families. Owing to linkage disequilibrium between alleles at the four markers, only three haplotypes are common in our sample. Using the transmission/disequilibrium test (TDT), we observed a strong bias for transmission of Haplotype 3 (1.1.1.2) from heterozygous parents to their affected children (P=0.008). Furthermore, using quantitative trait TDT analyses, we found significant and positive relationships between Haplotype 3 transmission and the inattentive symptoms, but not the hyperactive/impulsive symptoms, of ADHD. These findings support the proposed involvement of DRD1 in ADHD, and implicate Haplotype 3, in particular, as containing a potential risk factor for the inattentive symptom dimension of the disorder. Since none of the four marker alleles comprising Haplotype 3 is predicted to alter DRD1 function, we hypothesize that a functional DRD1 variant, conferring susceptibility to ADHD, is on this haplotype. To search for such a variant we screened the DRD1 coding region, by sequencing, focusing on the children who showed preferential transmission of Haplotype 3. DNA from 41 children was analysed, and no sequence variations were identified, indicating that the putative DRD1 risk variant for ADHD resides outside of the coding region of the gene.

Adolescent↗
PubMed2000

Association and linkage of DRD4 and DRD5 with attention deficit hyperactivity disorder (ADHD) in a sample of Turkish children.

The search for genetic factors predisposing to Attention Deficit Hyperactivity Disorder (ADHD) has focused on genes that regulate dopaminergic pathways such as dopamine receptors and enzymes that regulate levels of dopamine in the synapse. There have been several reports of association between ADHD and polymorphic variants within or near DRD4, DRD5, DAT1, DBH and COMT. In this study we set out to investigate specific alleles of DRD4 and DRD5, previously reported to be associated with ADHD, in a sample of Turkish children with DSM-IV ADHD children, as well as their relation to methylphenidate response and dimensional measures of symptom domains. One hundred and four independent trios and seven dyads were analysed using the transmission disequilibrium test (TDT). We found increased transmission of the DRD4 7-repeat allele (DRD4*7) (TDT chi2 = 2.79, P = 0.047). Given that we were testing specific a priori hypotheses regarding the associated alleles, we have used one-tailed P-values throughout. There was evidence of an interaction with methlyphenidate (MPH) response and analysis of the sample excluding non-responders revealed more significant evidence for the association (TDT chi2 = 4.48, P = 0.017). We also detected a trend for linkage and association in the DRD5 polymorphism (TDT chi2 = 2. 38, P = 0.06). Similar findings were obtained in relation to MPH response as analysis of MPH responders alone gave rise to a more significant association than that of the group as a whole (TDT chi2 = 4.9, P = 0.013). t-Test and logistic regression TDT analyses of DRD4*7 transmission with respect to dimensional rating scales of hyperactivity and impulsivity showed an inverse relation suggesting that in this sample DRD4*7 is associated with a lower level of ADHD symptomatology. While this may be due to stratification along a dimension of severity such that severe cases belong to a more extreme group with other specific genetic and environmental causes, similar to the model for low cognitive ability, it is more likely the result of a chance selection bias in this sample.

Alleles↗
PubMed1998

Validity of DSM-IV subtypes of conduct disorder based on age of onset.

OBJECTIVE: To present data from the DSM-IV field trials that led to the distinction between subtypes of conduct disorder (CD) that emerge in childhood or adolescence. In addition, data from a household sample were used to attempt to cross-validate these findings. METHOD: Differences between youths who met criteria for the two subtypes of CD were examined in the field trials sample of 440 youths aged 4 through 17 years and in a household sample of 1,285 youths aged 9 through 17 years. RESULTS: In both samples, there was a steep decline in aggression occurring around an age of onset of 10 years, but the number of nonaggressive behaviors was unrelated to the age of onset of CD. In the field trials sample, youths who met criteria for the adolescent-onset type were more likely to be girls, less likely to meet criteria for oppositional defiant disorder, and less likely to have a family history of antisocial behavior than the childhood-onset type, but these latter findings were not confirmed in the household sample. CONCLUSIONS: The DSM-IV approach to subtyping CD distinguishes subgroups that differ markedly in level of physical aggression. The advantages of a developmental approach to subtyping are discussed.

Adolescent↗
PubMed1997

Behavioral genetics '97: ASHG statement. Recent developments in human behavioral genetics: past accomplishments and future directions.

The field of behavioral genetics has enormous potential to uncover both genetic and environmental influences on normal and deviant behavior. Behavioral-genetic methods are based on a solid foundation of theories and methods that successfully have delineated components of complex traits in plants and animals. New resources are now available to dissect the genetic component of these complex traits. As specific genes are identified, we can begin to explore how these interact with environmental factors in development. How we interpret such findings, how we ask new questions, how we celebrate the knowledge, and how we use or misuse this knowledge are all important considerations. These issues are pervasive in all areas of human research, and they are especially salient in human behavioral genetics.

Adoption↗
PubMed1997

Attention-deficit hyperactivity disorder: a category or a continuum? Genetic analysis of a large-scale twin study.

OBJECTIVE: To investigate heritability and continuum versus categorical approaches to attention-deficit hyperactivity disorder (ADHD), using a large-scale twin sample. METHOD: A cohort of 1,938 families with twins and siblings aged 4 to 12 years, recruited from the Australian National Health and Medical Research Council Twin Registry, was assessed for ADHD using a DSM-III-R-based maternal rating scale. Probandwise concordance rates and correlations in monozygotic and dizygotic twins and siblings were calculated, and heritability was examined using the De Fries and Fulker regression technique. RESULTS: There was a narrow (additive) heritability of 0.75 to 0.91 which was robust across familial relationships (twin, sibling, and twin-sibling) and across definitions of ADHD as part of a continuum or as a disorder with various symptom cutoffs. There was no evidence for nonadditive genetic variation or for shared family environmental effects. CONCLUSIONS: These findings suggest that ADHD is best viewed as the extreme of a behavior that varies genetically throughout the entire population rather than as a disorder with discrete determinants. This has implications for the classification of ADHD and for the identification of genes for this behavior, as well as implications for diagnosis and treatment.

Attention Deficit Disorder with Hyperactivity↗
PubMed1997

Validity of the age-of-onset criterion for ADHD: a report from the DSM-IV field trials.

OBJECTIVE: To examine the validity of the DSM-IV requirement of an age of onset of impairment due to symptoms before 7 years of age for the diagnosis of attention-deficit/hyperactivity disorder (ADHD). METHOD: The validity of this criterion was examined in a clinic sample of 380 youths aged 4 through 17 years by comparing youths who met symptom criteria for ADHD and either did or did not display impairment before age 7 years. RESULTS: Nearly all youths who met symptom criteria for the predominantly hyperactive-impulsive subtype also met the age of onset of impairment criterion, but 18% of youths who met symptom criteria for the combined type, and 43% of youths who met symptom criteria for the predominantly inattentive type, did not manifest impairment before 7 years. For the latter two subtypes, requiring impairment before age 7 years reduced the accuracy of identification of currently impaired cases of ADHD and reduced agreement with clinicians' judgments. CONCLUSIONS: These findings raise questions about the validity of the DSM-IV definition of age of onset of ADHD. Marked differences in the ages of onset of both symptoms and impairment for the three subtypes of ADHD support the validity of distinguishing among these subtypes in DSM-IV.

Adolescent↗
PubMed1996

Twin sibling differences in parental reports of ADHD, speech, reading and behaviour problems.

Differences between twins and siblings in behaviour problems were investigated in a non-selected sample of 1938 families with children aged 4-12 years. Families were sent a questionnaire based on DSM-III-R criteria for Attention Deficit Hyperactivity Disorder (ADHD), Oppositional Defiant Disorder (ODD), Conduct Disorder (CD) and Separation Anxiety (SA), which was validated by formal clinical interview. The questionnaire also included measures of speech and reading problems. There were significant differences between twins and siblings for ADHD symptoms, but not for symptoms of ODD, CD or SA. Twins and siblings differed significantly for gestational age, birth weight, speech and reading problems. While there was little evidence for birth weight or gestational age contributing to the difference in ADHD symptoms, there was a strong association between ADHD symptoms and speech and reading problems.

Anxiety, Separation↗
PubMed1995

A novel comprehensive quality control instrument for medical accelerators.

A comprehensive quality control instrument for calibration of medical accelerators that use photon, electron, or proton beams in teleradiotherapy is described. It employs a fluorescence screen, mounted on a central stage with four degrees of freedom, monitored by a CCD camera. A single set-up of the instrument enables one to perform mechanical, light laser, and radiation tests, at arbitrary angles of the accelerator gantry. The new device provides for quantitative evaluation of the tests performed and provides for documentation of the test results in real time. The device provides significant time savings with concurrent improvement in accuracy for tests performed during installation and acceptance processes, and the implementation of quality control procedures for medical accelerators.

Electrons↗
PubMed1990

No difference in basal ganglia mineralization between schizophrenic and nonschizophrenic patients: a quantitative computerized tomographic study.

The role of iron in schizophrenia (SC) has aroused attention because of its modulatory effect on the dopamine receptor and its role as a cofactor for tyrosine hydroxylase. In addition, several postmortem studies suggest that increased mineralization (especially iron) of the basal ganglia is a possible clinicopathological correlate of schizophrenia. In order to quantitate the in vivo mineral content in the basal ganglia of patients with SC, a protocol was developed to analyze CT scans films with a LOATS computer analysis system. A total of 725 consecutive CT scans (275 SC, 450 nonSC) from a psychiatric population were reviewed. Eighteen scans (2.3%) revealed basal ganglia mineralization of which 7 cases carried a diagnosis of SC and 11 had other psychiatric disorders. All subjects had received neuroleptics, and 8 of the 11 patients in the nonschizophrenic group were demented. Both the SC and nonSC patients exhibited a prevalence (2.5%) of basal ganglia mineralization similar to that found in a postmortem series of the general population.

Adult↗
PubMed1982

The effect of lateral visual fixation on response latency to verbal and spatial questions.

The results of several studies have suggested a relationship between lateral eye movements and contralateral hemispheric activation or ipsilateral inhibition. The present study investigated the effects of lateral and central eye fixation on response latency to verbal and spatial questions. Response latencies for verbal questions were significantly longer when subjects fixated to the left or centrally, as compared to the right. On spatial questions, response latencies were significantly longer in the right fixation condition than in the other conditions. The results indicate that visual fixation ipsilateral to hemispheric activation is related to slower problem solving, and suggest that eye movements during cognitive activity may have functional significance.

Cerebral Cortex↗
PubMed1978

Lymphosarcoma in an ectopic pelvic spleen.

Wandering spleen is a rare condition which can be diagnosed with facility by conventional nuclear medicine imaging techniques. We present one case in which generalized lymphosarcoma involving a wandering spleen was proved by percutaneous aspiration biopsy. Evaluation of a liver-spleen scan in which the normal splenic image is not definitely seen should include extension of the scan field to include the lower abdomen, because of the possibility of ectopic splenic position.

Aged↗