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Biomedical subjects

A E Doyle

Publications and source records attributed to A E Doyle.

At least 19 recordsLinked to original sources
PubMed2007

A study of how socioeconomic status moderates the relationship between SNPs encompassing BDNF and ADHD symptom counts in ADHD families.

Recent animal research suggests that brain-derived neurotrophic factor (BDNF), may mediate response to different environmental stimuli. In this paper, we evaluated the possible role of BDNF as a moderator of attention deficit hyperactivity disorder (ADHD) in the context of different socioeconomic classes. We genotyped ten single nucleotide polymorphisms (SNPs) in and around BDNF in 229 families and evaluate whether there are SNP-by-socioeconomic status (SES) interactions for attention deficit hyperactivity. We developed three quantitative phenotypes for ADHD from nine inattentive and nine hyperactive-impulsive symptoms that were used in SNP-by-SES interaction analyses using a new methodology implemented in the computer program PBAT. Findings were adjusted for multiple comparisons using the false discovery rate. We found multiple significant SNP-by-SES interactions using the inattentive symptom count. This study suggests that different SES classes may modify the effect of the functional variant(s) in and around BDNF to have an impact on the number of ADHD symptom counts that are observed. The two exons within BDNF represent potential functional variants that may be causing the observed associations.

Attention Deficit Disorder with Hyperactivity↗
PubMed2001

A family study of psychiatric comorbidity in girls and boys with attention-deficit/hyperactivity disorder.

BACKGROUND: Because attention-deficit/hyperactivity disorder (ADHD) is relatively infrequent among girls, little is known about the nature and causes of psychiatric comorbidity in girls and the reason for gender differences in the prevalence of these comorbidities. METHODS: Using blinded, structured psychiatric interviews, we studied two groups of boys: 140 ADHD probands and 120 non-ADHD comparisons. These groups had 454 and 368 first-degree biological relatives, respectively. We also studied two groups of girls: 140 ADHD probands and 122 non-ADHD comparisons. These groups had 417 and 369 first-degree biological relatives, respectively. RESULTS: The co-occurrence of ADHD and comorbid psychopathology in families was the same for families ascertained through boy and girl probands. CONCLUSIONS: Our results suggest that boys and girls do not differ in the familial risk factors that mediate comorbid psychopathology and the familial aggregation of comorbid disorders in ADHD families. Although this is consistent with prior work suggesting more similarities than differences in the nature of psychiatric comorbidity in ADHD boys and girls, we cannot make strong conclusions, owing to the possibility of cohort effects.

Adolescent↗
PubMed2001

Learning disabilities and executive dysfunction in boys with attention-deficit/hyperactivity disorder.

The effect of comorbid reading or arithmetic learning disabilities (LDs) on neuropsychological function in attention-deficit/hyperactivity disorder (ADHD) was studied. Participants were young males diagnosed with ADHD, with and without LD, and non-ADHD, non-LD male controls of similar age. LD was defined by combined regression-based and low-achievement classifications. Analyses adjusted for the effect of psychiatric comorbidity, age, and socioeconomic status on neuropsychological function. Children who had both ADHD and LD were significantly more impaired on both executive and nonexecutive functions than ADHD children without LD. Neuropsychological performance was most impaired in ADHD with combined arithmetic and reading disability. These data indicate that comorbid LD, especially arithmetic disability, significantly increases the severity of executive function impairment in ADHD.

Adolescent↗
PubMed2001

Separating attention deficit hyperactivity disorder and learning disabilities in girls: a familial risk analysis.

OBJECTIVE: Familial risk analysis was used to clarify the relationship in girls between attention deficit hyperactivity disorder (ADHD) and learning disabilities in either mathematics or reading. METHOD: The authors assessed the presence of ADHD and learning disabilities in 679 first-degree relatives of three groups of index children: girls with ADHD and a comorbid learning disability, girls with ADHD but no learning disabilities, and a comparison group of girls without ADHD. RESULTS: The risk for ADHD was similarly higher in families of ADHD probands with and without learning disabilities; both groups had significantly higher rates of ADHD than did families of the comparison girls. In contrast, only among relatives of ADHD probands with a learning disability was there a higher risk for learning disabilities. A strong (although statistically nonsignificant) difference emerged that suggested at least some degree of cosegregation of ADHD and learning disabilities in family members. There was no evidence of nonrandom mating between spouses with ADHD and learning disabilities. CONCLUSIONS: These results extend previously reported findings regarding the relationship of ADHD and learning disabilities to female subjects and raise the possibility that, in girls, the relationship between ADHD and learning disabilities is due to shared familial risk factors.

Adolescent↗
PubMed2001

Meta-analysis of the association between the 7-repeat allele of the dopamine D(4) receptor gene and attention deficit hyperactivity disorder.

OBJECTIVE: Family, twin, and adoption studies show attention deficit hyperactivity disorder (ADHD) to have a substantial genetic component. Although several studies have shown an association between ADHD and the 7-repeat allele of the dopamine D(4) receptor gene (DRD4), several studies have not. Thus, the status of the ADHD-DRD4 association is uncertain. METHOD: Meta-analysis was applied to case-control and family-based studies of the association between ADHD and DRD4 to assess the joint evidence for the association, the influence of individual studies, and evidence for publication bias. RESULTS: For both the case-control and family-based studies, the authors found 1) support for the association between ADHD and DRD4, 2) no evidence that this association was accounted for by any one study, and 3) no evidence for publication bias. CONCLUSIONS: Although the association between ADHD and DRD4 is small, these results suggest that it is real. Further studies are needed to clarify what variant of DRD4 (or some nearby gene) accounts for this association.

Adolescent↗
PubMed2001

Long-term stability of the Child Behavior Checklist in a clinical sample of youth with attention deficit hyperactivity disorder.

Evaluated the long-term stability of the Child Behavior Checklist (CBCL) in a longitudinal clinical sample of youth with attention deficit hyperactivity disorder (ADHD), testing the hypothesis that the CBCL scales will show stability over time. Participants were 105 Caucasian, non-Hispanic boys with ADHD between the ages of 6 and 17 assessed at baseline and at a 4-year follow-up. Stability of CBCL scales were computed for dimensional (intraclass correlation coefficients [ICCs], Pearson correlations) and dichotomized scale scores (kappa coefficients and odds ratios [ORs]). Evidence was found for stability of the categorical and dimensional types of scores, as demonstrated by statistically significant stability of the Pearson correlation coefficients, kappas, and ORs. The robust findings obtained from ICCs and kappa coefficients document substantial stability for CBCL scales over time within individuals with ADHD. These results support the informativeness of the CBCL as a useful measure of longitudinal course in clinical samples of youth with ADHD.

Adolescent↗
PubMed2001

The nature and heritability of attention-deficit/hyperactivity disorder.

This article reviews family, twin, and adoption studies, along with segregation analyses and molecular genetic studies, suggesting that both genetic and environmental factors contribute to the etiology of ADHD. Findings also indicate that the genetic mechanisms that predispose individuals to ADHD are likely to be complex, and the literature on ADHD raises many questions regarding clinical and pathophysiologic heterogeneity of the disorder. Although there is no single pathophysiologic profile of ADHD, data do implicate dysfunction in the frontosubcortical pathways that control attention and motor behavior. Moreover, the effectiveness of stimulants, along with animal models of hyperactivity, point to catecholamine dysregulation as at least one source of ADHD brain dysfunction.

Adolescent↗
PubMed2000

Attention-deficit/hyperactivity disorder in adults: an overview.

To assess the validity of adult attention-deficit/hyperactivity disorder (ADHD), we reviewed clinical, family, psychopharmacologic, neurobiological, and outcome studies. We found multiple reports describing adults with clinical features highly reminiscent of the childhood ADHD. These adults, who are impulsive, inattentive, and restless, have the clinical "look and feel" of ADHD children. As with their childhood counterparts, many adults with ADHD suffer from antisocial, depressive, and anxiety disorders. They also show clinically significant impairments--histories of school failure, occupational problems, and traffic accidents. Studies of biological features show correspondences between child and adult cases of ADHD. Both show familial aggregation and a characteristic profile of neuropsychologic deficits; an emerging neuroimaging literature suggests that abnormalities in the same brain regions underlie both the child and adult forms of the disorder. Although these converging lines of evidence support the validity of ADHD in adults, follow-up studies of ADHD children have yielded ambiguous results. This ambiguity is in part due to differences in how researchers define the persistence of ADHD, a problem that suggests future research focus on how best to diagnose ADHD in adulthood.

Adult↗
PubMed2000

Genetic influences on attention deficit hyperactivity disorder.

In this article we review behavioral and molecular genetics studies of attention deficit hyperactivity disorder (ADHD). Family, twin, and adoption studies, along with segregation analyses and molecular genetic studies, all support the hypothesis that both genetic and environmental factors contribute to the etiology of ADHD. Despite this strong evidence for the familial transmission of ADHD, the mode of transmission requires further clarification. In addition, because ADHD appears to be genetically heterogeneous, more work is needed to delineate genetically homogeneous subtypes and describe the range of expression of their underlying genotypes.

Adolescent↗
PubMed1999

Toward a transactional conceptualization of oppositional defiant disorder: implications for assessment and treatment.

The conceptualization and treatment of oppositional defiant disorder (ODD) has been characterized by surprising homogeneity. In this paper evidence is presented to underscore the heterogeneity within ODD, including research demonstrating (a) the distinction between reactive and proactive forms of aggression; (b) the importance of affective modulation and self-regulation, and associated cognitive skills, in the development of the skill of compliance; and (c) high levels of comorbidity between ODD and other disorders. The disparate pathways that give rise to oppositional behavior suggest that different children with ODD may require different forms of intervention. The necessity of a transactional conceptualization, of achieving a comprehensive understanding of the factors underlying the difficulties of individual children with ODD, and of matching intervention ingredients to the specific needs of different children and families is discussed.

Age Factors↗
PubMed1995

Comparison of effects of ACE inhibition with calcium channel blockade on renal disease in a model combining genetic hypertension and diabetes.

The aim of this study was to compare the renal effects of angiotensin converting enzyme (ACE) inhibition with calcium channel blockade in a model combining genetic hypertension with diabetes. Streptozotocin diabetes was induced in spontaneously hypertensive rats (SHR). The animals were then randomized to receive no treatment, the ACE inhibitor, perindopril, or the dihydropyridine calcium antagonist lacidipine. Body weight, systolic blood pressure, glycemic control, renal function, and albumin excretion rate (AER) were assessed serially over the 32-week study period. At week 32 the animals were killed and glomerular volume was measured. Both antihypertensive regimens significantly reduced systolic blood pressure in diabetic SHR. There was no significant difference in glycemic control, serum creatinine, or glomerular filtration rate among the three groups at week 32. The ACE inhibitor perindopril significantly reduced AER and glomerular hypertrophy over the 32 weeks, whereas the calcium antagonist lacidipine failed to reduce AER or glomerular hypertrophy. Thus, in contrast to the effects of ACE inhibition, calcium channel blockade with lacidipine, despite significantly reducing blood pressure, failed to reduce renal injury in this model. These results support the hypothesis that antihypertensive regimens may differ in their capacity to protect the diabetic kidney, despite similar effects on systemic blood pressure.

Albuminuria↗
PubMed1994

The paradoxical effect of diet commercials on reinhibition of dietary restraint.

Although many studies have explored the mechanism by which dietary restraint becomes disinhibited, few have examined how restraint is restored or "reinhibited." Using a taste test with preload design, we showed a sad movie clip interrupted by diet-related commercials, neutral commercials, or no commercials to women with high and low restraint scores. We predicted that images of successful dieting would foster reinhibition. Results, however, revealed the opposite: high restrained eaters who viewed the diet-oriented commercials ate more than other subjects. We interpret these data as suggesting that diet-related images act as additional disinhibitors and view our results in light of research linking ego threat to dietary disinhibition (Heatherton, Herman, & Polivy, 1991).

Advertising↗
PubMed1993

A review of the short-term benefits of antihypertensive treatment with emphasis on stroke.

Hypertension is the major underlying risk factor for stroke, and the risk of stroke increases proportionally to the rise in blood pressure. In the elderly, systolic hypertension increases the risk of stroke. Stroke in hypertensive patients may be due to Charcot-Bouchard aneurysm, to atherosclerosis of the extracranial and major cerebral arteries, or to embolism as a result of cardiac disease. Reduction of blood pressure greatly reduces the risk of stroke in severe, mild-to-moderate, and isolated systolic hypertension. The reduction in stroke risk occurs up to a year after the onset of treatment and appears to persist thereafter. The use of dihydropyridine calcium antagonists may confer further benefits in addition to those related to blood pressure reduction as these agents block the influx of calcium into ischemic brain cells, thereby limiting the extent of the infarction. However, although these effects have been impressive in experimental models, there is as yet no convincing evidence of this effect in clinical studies.

Aged↗
PubMed1993

Angiotensin II, sodium, and cardiovascular hypertrophy in spontaneously hypertensive rats.

Angiotensin II (Ang II) may cause cardiovascular hypertrophy as a consequence of increased blood pressure or possibly by direct trophic actions. To dissociate Ang II and blood pressure in young spontaneously hypertensive rats (SHR), we used sodium loading during angiotensin converting enzyme inhibitor treatment. Animals were treated between 6 and 10 weeks of age with perindopril to lower Ang II and blood pressure, or with perindopril and 1% saline drinking fluid or perindopril and aldosterone infusion to lower Ang II but maintain high blood pressure. Blood pressure, heart weight, and media/lumen ratio of mesenteric resistance arteries were studied while rats were on treatment at 10 weeks of age and 15 weeks after treatment at 25 weeks of age. Perindopril lowered blood pressure and inhibited the development of cardiovascular hypertrophy. Saline or aldosterone restored high blood pressure during perindopril treatment and resulted in increased heart weight/body weight and resistance artery media/lumen ratios in direct proportion to the elevation of blood pressure. Because increased structure occurred despite perindopril treatment, we conclude that direct trophic actions of Ang II are not essential for the development of cardiovascular hypertrophy in young SHR and that the antitrophic actions of angiotensin converting enzyme inhibitors depend more on changes in blood pressure than on Ang II. However, restoration of blood pressure and structure by sodium during perindopril treatment raises the possibility that the design of the cardiovascular system and blood pressure may depend indirectly on Ang II through effects on sodium metabolism.

Angiotensin II↗
PubMed1993

The effects of perindopril and triple therapy in a normotensive model of diabetic nephropathy.

The effect of the angiotensin-converting enzyme inhibitor, perindopril, on functional and structural parameters of diabetic nephropathy has been compared with triple therapy (hydralazine, reserpine, and hydrochlorothiazide) in normotensive, STZ-induced diabetic Sprague-Dawley rats. Animal groups included control rats, diabetic rats treated with perindopril, diabetic rats receiving triple therapy, and untreated diabetic rats. Treatment was continued for 32 wk. Blood pressure reduction and severity of diabetes, as assessed by body weight and glycemic control were similar with both drug regimens. A similar rise in plasma renin activity occurred in the two groups receiving antihypertensive drugs, whereas the perindopril but not the triple therapy group had suppressed plasma angiotensin-converting enzyme activity. No significant difference was observed in renal function among the four groups. Diabetes was associated with a progressive increase in albuminuria, but this rise was ameliorated by both perindopril and triple therapy. No significant difference was noted in albuminuria between triple therapy and perindopril-treated diabetic rats. Diabetes was associated with glomerular basement membrane thickening, mesangial expansion, and glomerular volume. No glomerular ultrastructural parameter was affected by antihypertensive drugs. No specific benefit of angiotensin-converting enzyme inhibition over triple therapy could be detected in this normotensive model of diabetic nephropathy.

Analysis of Variance↗
PubMed1992

Antihypertensive therapy in a model combining spontaneous hypertension with diabetes.

We have compared the effects of the angiotensin converting enzyme inhibitor, perindopril, and a conventional antihypertensive regimen (triple therapy: hydralazine, reserpine and hydrochlorothiazide) on kidney function and albuminuria in hypertensive diabetic rats. Diabetes was induced with streptozotocin in spontaneously hypertensive (SHR) rats and they were randomized to receive no treatment, perindopril or triple therapy. Antihypertensive drugs were commenced at the time of induction of diabetes and continued for 16 weeks. Blood pressure reduction was equal in the groups treated with perindopril or triple therapy. All groups had similar severity of diabetes as determined by body weight, serum glucose and glycated hemoglobin levels. Whereas plasma renin activity rose in both the perindopril and triple therapy groups, it is likely that the effects on angiotensin II levels were opposite since perindopril but not triple therapy was associated with a significant reduction in plasma angiotensin converting enzyme activity. Diabetes was associated with an increase in glomerular filtration rate. At 12 weeks, glomerular filtration rate was higher in the perindopril treated group when compared to the triple therapy group, but neither group treated with antihypertensive therapy was different to untreated diabetic rats. Both drug regimens reduced albuminuria in the diabetic rats to a similar degree apparently independently of their effects on the renin-angiotensin system. Studies in diabetic subjects are warranted to evaluate different classes of antihypertensive drugs with respect to their effects on kidney function, proteinuria and glomerular morphology.

Albuminuria↗