Biomedical subjects

Megan Aleardi

Publications and source records attributed to Megan Aleardi.

17 recordsLinked to original sources

PubMed2006

Mania, glutamate/glutamine and risperidone in pediatric bipolar disorder: a proton magnetic resonance spectroscopy study of the anterior cingulate cortex.

BACKGROUND: The purpose of this study was to investigate the anterior cingulate cortex (ACC) glutamate/glutamine (Glx) to creatine ratio (Glx/Cr) in two groups of children with Bipolar Disorder (BPD): those exhibiting manic symptoms requiring treatment and those being stably treated with the atypical antipsychotic risperidone. Atypical antipsychotics have been shown to increase serum glutamate levels and ACC Glx/Cr in subjects with schizophrenia. In this study, we hypothesized that the children with BPD in need of treatment would have lower Glx/Cr compared with the children with BPD being stably treated with risperidone. METHODS: Proton MR spectra were acquired, at 1.5 T, from the ACC of eighteen subjects with a DSM-IV diagnosis of BPD: ten (11.10+/-3.48 years; five female) were manic and not medicated with any antipsychotic and eight (10.88+/-2.99 years; one female) were medicated with the atypical antipsychotic risperidone. RESULTS: Children with BPD exhibiting manic symptoms requiring treatment had lower Glx/Cr than children with BPD being stably treated with the atypical antipsychotic risperidone. The children treated with risperidone also had significantly lower YMRS and CGI-Mania scores than the children not treated with risperidone. Both YMRS and CGI-Mania scores correlated negatively with ACC Glx/Cr levels. LIMITATIONS: The cross-sectional design, small sample size, the use of Glx rather than glutamate or glutamine and the use of Cr ratios rather than absolute concentrations are limitations of this study. CONCLUSIONS: Children with mania have lower Glx/Cr levels than children with BPD being stably treated with the atypical antipsychotic risperidone. Mania may be associated with reduced glutamate/glutamine levels in the ACC: other imaging studies have shown mania associated with hypometabolism in the ACC. These reductions in glutamate/glutamine may be increased following successful treatment with glutamatergic agents.

Adolescent↗

PubMed2006

An open-label trial of OROS methylphenidate in adults with late-onset ADHD.

INTRODUCTION: Many adults with current impairing symptoms of attention-deficit/hyperactivity disorder (ADHD) do not report an age at onset before 7 years of age and cannot, therefore, be assigned the full Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), diagnosis of ADHD. We hypothesized that treatment with oral release osmotic system (OROS) methylphenidate (MPH) will be safe and efficacious for the treatment of adults with late-onset ADHD. METHOD: This was a 6-week, open-label, prospective treatment study of OROS MPH monotherapy in 36 adult patients with late-onset ADHD (onset later than the required 7 years of age) using standardized instruments for diagnosis and a robust oral daily dose of up to 1.3 mg/kg/day. Symptom severity was assessed with the Adult ADHD Investigator Symptom Report Scale (AISRS) and the Clinical Global Impression (CGI) scale. RESULTS: Subjects reported robust current symptoms of ADHD at pre-treatment baseline (11.1+/-2.8 DSM-IV symptoms), but had an atypical mean age at onset of 14.2+/-8.6 years. Treatment with OROS MPH at an average daily dose of 78.2+/-29.4 mg was associated with a statistically and clinically significant reduction in ADHD symptoms relative to baseline as assessed through the AISRS (-16.4+/-10.5; P<.001). Using a categorical definition of response (CGI-I much or very much improved), a majority (n = 26; 72%) of subjects were rated as improved at endpoint. CONCLUSION: These results extend previous findings in adults with full ADHD to adults meeting criteria for late-onset ADHD and support the need for further controlled clinical trials in this population.

Adolescent↗

PubMed2006

A double-blind comparison of galantamine hydrogen bromide and placebo in adults with attention-deficit/hyperactivity disorder: a pilot study.

BACKGROUND: Galantamine hydrogen bromide (HBr) is a competitive and reversible inhibitor of acetylcholinesterase. Because of its cholinergic nicotinic mechanism of action, galantamine HBr was hypothesized to have therapeutic activity in the treatment of attention-deficit/hyperactivity disorder (ADHD). METHOD: We conducted a 12-week, double-blind, placebo-controlled, randomized clinical trial using daily doses of up to 24 mg/d of galantamine HBr in the treatment of adults who met full Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for ADHD with childhood-onset and persistent adult symptoms. All analyses were intention to treat with the last observation carried forward for subjects who did not complete the full study schedule. RESULTS: The mean daily doses at week 12 were 19.8 +/- 6.4 mg for galantamine HBr and 21.8 +/- 4.6 mg for placebo (P = 0.3). There was no statistically or clinically significant greater reduction in ADHD symptoms in subjects treated with galantamine HBr relative to those receiving placebo (P = 0.5). Using last observation carried forward, 4 (22%) of 18 of patients receiving galantamine HBr were considered responders (much or very much improved on the Clinical Global Impression Improvement Scale and at least a 30% reduction on the ADHD Investigator Symptom Report Scale compared with 11% [2/18] on placebo; P = 0.4). CONCLUSION: These results do not support the clinical utility of galantamine HBr in the treatment of ADHD at the doses used in this pilot study.

Adolescent↗

PubMed2006

Differences in brain chemistry in children and adolescents with attention deficit hyperactivity disorder with and without comorbid bipolar disorder: a proton magnetic resonance spectroscopy study.

OBJECTIVE: The authors' goal was to investigate phosphatidylinositol and glutamatergic metabolism in the anterior cingulate cortex of children and adolescents with attention deficit hyperactivity disorder (ADHD) alone, children with ADHD plus bipolar disorder, and children with no axis I diagnosis. METHOD: Proton spectra were acquired from a 4.8-ml voxel placed in the anterior cingulate cortex of 30 subjects who were 6 to 13 years old. Fifteen subjects had ADHD and no comorbid disorder, eight had ADHD plus bipolar disorder, and seven were healthy comparison subjects. RESULTS: Children with ADHD had a significantly higher ratio of glutamate plus glutamine to myo-inositol-containing compounds than children with ADHD plus bipolar disorder and healthy children. CONCLUSIONS: myo-Inositol-containing compounds may provide information on the action of antimanic treatments such as lithium, valproate, and carbamazepine. Glutamate and glutamine are measures of glutamatergic neurotransmission and thus may also reflect changes in serotonin and dopamine pathways.

Adolescent↗

PubMed2006

Adults with ADHD and sleep complaints: a pilot study identifying sleep-disordered breathing using polysomnography and sleep quality assessment.

OBJECTIVE: ADHD and sleep-disordered breathing are both prevalent in adulthood. Because both conditions may be responsible for similar symptoms of cognitive impairment, the authors investigate whether their presentation may overlap in adults diagnosed with ADHD. METHOD: Data are collected from six adults with sleep complaints who were diagnosed with ADHD using rigorous clinical criteria. All participants undergo overnight polysomnography and complete questionnaires about sleep quality, circadian sleep pattern, and daytime fatigue. RESULTS: On standardized measures, all participants report poor sleep quality, two report daytime fatigue, and none report distinct deviation from normal sleep and wake cycle pattern. Polysomnography reveals evidence of sleep-disordered breathing and sleep fragmentation in all participants. CONCLUSION: Objective evidence of breathing-related sleep disorders can be found in some adults with carefully diagnosed ADHD who report sleep complaints. This report highlights the importance of identifying treatable sleep disorder comorbidity in adults with ADHD.

Adult↗

PubMed2006

Functional impairments in adults with self-reports of diagnosed ADHD: A controlled study of 1001 adults in the community.

OBJECTIVE: The objective of this study was to evaluate functional impairments in a nonreferred sample of adults identifying themselves as having been diagnosed with attention-deficit/hyperactivity disorder (ADHD) by a clinician in their community. METHOD: We completed a survey in April and May 2003 of a community sample of 500 adults who reported having received a diagnosis of ADHD in the community and 501 gender- and age-matched comparisons from a national sample representative of the U.S. population. RESULTS: Adults with self-reports of diagnosed ADHD in the community were significantly less likely to have graduated high school (83% vs. 93% of controls; p < or = .001) or obtain a college degree (19% vs. 26%; p < .01), were less likely to be currently employed (52% vs. 72%; p < or = .001), and had significantly more mean job changes over 10 years (5.4 vs. 3.4 jobs; p < or = .001). They also were significantly more likely to have been arrested (37% vs. 18% of controls; p < or = .001) or divorced (28% vs. 15%; p < or = .001) and were significantly less satisfied (p < or = .001) with their family, social, and professional lives. CONCLUSION: Adults who reported having received a diagnosis of ADHD in the community had significant impairment in multiple domains of functioning compared with age- and gender-matched controls without this diagnosis, highly consistent with findings derived from carefully diagnosed referred samples.

Adolescent↗

PubMed2006

Characterizing impaired driving in adults with attention-deficit/hyperactivity disorder: A controlled study.

OBJECTIVE: We sought to confirm previously documented findings that individuals with attention-deficit/hyperactivity disorder (ADHD) demonstrate impaired driving behavior when compared with controls. METHOD: Subjects were adults with (N = 26) and without (N = 23) DSM-IV ADHD ascertained through clinical referrals to an adult ADHD program and through advertisements in the local media. Driving behavior was assessed using the Manchester Driving Behavior Questionnaire (DBQ) and 10 questions from a driving history questionnaire. Neuropsychological testing and structured interviews were also administered to all subjects. RESULTS: Substantially more ADHD subjects had been in an accident on the highway (35% vs. 9%, p = .03) or had been rear-ended (50% vs. 17%, p = .02) compared with controls. Analysis of the DBQ findings showed that ADHD subjects had significantly higher mean +/- SD scores than control subjects on the total DBQ (34.1 +/- 15.2 vs. 18.0 +/- 8.6, p < .001) and in all 3 subscales of the DBQ: errors (9.3 +/- 5.4 vs. 4.6 +/- 3.5, p < .001), lapses (12.4 +/- 6.2 vs. 6.1 +/- 3.5, p < .001), and violations (12.4 +/- 5.2 vs. 7.4 +/- 4.1, p < .001). Using the score that separated ADHD from control drivers on the DBQ as a cutoff, ADHD drivers at high risk for poor driving outcomes had more severe rates of comorbidity and exhibited more impaired scores on neuropsychological testing. CONCLUSIONS: Our results confirm and extend previous work documenting impaired driving behavior in subjects with ADHD. Results also suggest that ADHD individuals at high risk for poor driving behavior might be distinguishable from other ADHD individuals on DBQ scores, neuropsychological deficits, and patterns of comorbidities.

Accidents, Traffic↗

PubMed2005

A randomized, placebo-controlled trial of OROS methylphenidate in adults with attention-deficit/hyperactivity disorder.

BACKGROUND: The objective of this study was to evaluate the safety and efficacy of once-daily OROS methylphenidate (MPH) in the treatment of adults with DSM-IV attention-deficit/hyperactivity disorder (ADHD). METHODS: We conducted a randomized, 6-week, placebo-controlled, parallel-design study of OROS MPH in 141 adult subjects with DSM-IV ADHD, using standardized instruments for diagnosis. OROS MPH or placebo was initiated at 36 mg/day and titrated to optimal response, depending on efficacy and tolerability, up to 1.3 mg/kg/day. RESULTS: Treatment with OROS MPH was associated with clinically and statistically significant reductions in DSM-IV symptoms of inattention and hyperactivity/impulsivity relative to subjects treated with placebo. At endpoint, 66% of subjects (n = 44) receiving OROS MPH and 39% of subjects (n = 29) [corrected] receiving placebo attained our a priori definition of response of much or very much improved on the Clinical Global Impression-Improvement scale plus a >30% reduction in Adult ADHD Investigator System Report Scale score. OROS MPH was associated with small but statistically significant increases in systolic blood pressure (3.5 +/- 11.8 mm Hg), diastolic blood pressure (4.0 +/- 8.5 mm Hg), and heart rate (4.5 +/- 10.5 bpm). CONCLUSIONS: These results show that treatment with OROS MPH in daily doses of up to 1.3 mg/kg/day was effective in the treatment of adults with ADHD. Because of the potential for increases in blood pressure and heart rate, subjects receiving treatment with MPH should be monitored for changes in blood pressure parameters during treatment.

Adult↗

PubMed2005

Open-label, 8-week trial of olanzapine and risperidone for the treatment of bipolar disorder in preschool-age children.

BACKGROUND: To evaluate short-term safety and efficacy of atypical antipsychotics in a single-site, prospective, open-label, 8-week study of risperidone and olanzapine monotherapy in preschoolers with bipolar disorder (BPD). METHODS: Risperidone was initiated at an open-label dose of .25 mg/day, increased weekly according to response and tolerability to a maximum does of 2.0 mg/day. Olanzapine was initiated at 1.25 mg/day and increased to no more than 10 mg/day. RESULTS: Thirty-one children aged 4-6 years were treated with olanzapine (n = 15, 6.3 +/- 2.3 mg/day) or risperidone (n = 16, 1.4 +/- .5 mg/day). At study end point (week 8 or last observation carried forward), there was a 18.3 +/- 11.9 point (t = -5.6, p < .001) reduction in risperidone-treated subjects and a 12.1 +/- 10.4 point (t = -4.4, p < .001) reduction in Young Mania Rating Scale (YMRS) scores in olanzapine-treated subjects that did not differ between groups (t = 1.4, p = .2). Response criteria (Clinical Global Impression improvement of "Much" or "Very Much" improved or a YMRS change of >or= 30% or more) indicated no difference in rate of response with risperidone and olanzapine (69% vs. 53%, chi(2)((1)) = .8, p = .4). CONCLUSIONS: This prospective open study suggests that treatment with risperidone or olanzapine may result in a rapid reduction of symptoms of mania in preschool children with BPD. Because of substantial residual symptomatology and adverse effects, however, a pressing need exists to identify additional safe and effective treatments for the management of BPD in this high-risk population.

Antipsychotic Agents↗

PubMed2005

Behavior differences in drivers with attention deficit hyperactivity disorder: the driving behavior questionnaire.

Attention deficit hyperactivity disorder (ADHD) has been linked to an increased number of driving citations, especially for speeding and a four-fold increase in accident risk. Using three factors--errors, lapses and violations--found in prior work, we ran regression analyses to explore the impact of ADHD status, gender and age on error, lapse and violation report scores. The results indicate that ADHD status is positively and significantly related to error, lapse and violation scores. In the cases of errors and violations, however, interactions between ADHD status and age are significant such that older participants with ADHD do not differ statistically from controls. There were no significant effects of age on error, lapse or violation scores for control participants. Consistent with earlier work, gender was significantly related to violation scores, but not to errors or lapses, such that men were more likely than women to report higher violation scores, controlling for ADHD status and age. We consider possible explanations for these findings and discuss the implications of these results for the accident risk of individuals with ADHD as they age.

Adult↗

PubMed2005

A large, double-blind, randomized clinical trial of methylphenidate in the treatment of adults with attention-deficit/hyperactivity disorder.

BACKGROUND: The few controlled studies of methylphenidate (MPH) in adults with attention deficit/hyperactivity disorder (ADHD) have reported equivocal results. A previous, pilot study by our group suggested that these results were due to inadequate dosing. METHOD: We conducted a randomized, 6-week, placebo-controlled, parallel study of MPH in 146 adult patients with DSM-IV ADHD using standardized instruments for diagnosis, separate assessments of ADHD, depressive and anxiety symptoms, and a robust average oral daily dose of 1.1 mg/kg/day. RESULTS: We found a marked therapeutic response for the MPH treatment of ADHD symptoms that exceeded the placebo response (76% vs. 19%). Treatment was safe and well tolerated. Response to MPH was independent of socioeconomic status, gender, and lifetime history of psychiatric comorbidity. CONCLUSIONS: These results confirm that robust doses of MPH are effective in the treatment of adult ADHD.

Adult↗

PubMed2005

Aripiprazole in the treatment of pediatric bipolar disorder: a systematic chart review.

BACKGROUND: Pediatric bipolar disorder is a serious neuropsychiatric disorder associated with high levels of morbidity and disability. OBJECTIVE: This is a systematic chart review of all outpatient youth with the diagnosis of bipolar disorder and bipolar spectrum disorder treated with aripiprazole either alone or as add-on to ongoing treatments. METHOD: Medical records were reviewed to identify all subjects with bipolar and bipolar spectrum disorder prescribed aripiprazole in our clinic. During the chart review, the Clinical Global Impression scale was completed by the treating clinicians to determine usefulness. RESULTS: Forty-one youths (mean age+/-SD: 11.4+/-3.5 years) with bipolar spectrum disorder who had been treated with aripiprazole were identified. These children received a mean daily dose of aripiprazole 16.0+/-7.9 mg over an average of 4.6 months. Using a Clinical Global Impression-Improvement scale score of <2 (very much/much improved) to define robust improvement, 71% showed improvement in manic symptoms. Treatment with aripiprazole was well tolerated. CONCLUSION: This study suggests that aripiprazole may be a useful and well-tolerated treatment for youth with bipolar disorder and it supports the need for controlled clinical trials of this compound in juvenile mania.

Adolescent↗

PubMed2005

An open-label trial of risperidone in children and adolescents with bipolar disorder.

OBJECTIVE: The aim of this study was to evaluate the potential of risperidone as a treatment of pediatric bipolar disorder. METHODS: This was an 8-week, open-label, prospective study of risperidone monotherapy (1.25 +/- 1.5 mg/d) for 30 bipolar youths (manic, mixed, or hypomanic; 6-17 years of age). RESULTS: Twenty-two of the 30 youths (73%) completed the study. Using predefined criteria for improvement (a Clinical Global Impressions Improvement in Mania score of < or =2 at endpoint), the response rate for manic symptoms was 70%. The significant reduction in symptoms of mania resulted in a mean Young Mania Rating Scale (YMRS) score 13.5 at endpoint, indicating mild residual symptoms. Weight increased significantly from baseline (2.1 +/- 2.0 kg; p < 0.001) and there was a four-fold increase in prolactin levels from baseline (p < 0.001). CONCLUSIONS: Open-label risperidone treatment was associated with a significant shortterm improvement of symptoms of pediatric bipolar disorder. Future placebo-controlled, double-blind studies are needed to confirm these preliminary results.

Adolescent↗

PubMed2005

Absence of gender effects on attention deficit hyperactivity disorder: findings in nonreferred subjects.

OBJECTIVE: In a previous study, the authors found that, compared with referred boys with attention deficit hyperactivity disorder (ADHD), girls are less likely to manifest comorbid disruptive behavior disorders and learning disabilities--characteristics that could adversely affect identification of ADHD in girls. However, because referral bias can affect outcome, these findings require replication in nonreferred groups of ADHD subjects. METHOD: The authors evaluated gender effects in a large group of nonreferred siblings (N=577) of probands with ADHD and non-ADHD comparison subjects. Ninety-eight of the nonreferred siblings (N=73 males, N=25 females) met the criteria for diagnosis of ADHD, and 479 (N=244 males, N=235 females) did not meet those criteria. All siblings were systematically and comprehensively assessed with measures of emotional, school, intellectual, interpersonal, and family functioning. The assessment battery used for the siblings was the same as that used for the probands. RESULTS: The nonreferred males and females with ADHD did not differ in DSM-IV subtypes of ADHD, psychiatric comorbidity, or treatment history. They also showed similar levels of cognitive, psychosocial, school, and family functioning. CONCLUSIONS: These findings suggest that the clinical correlates of ADHD are not influenced by gender and that gender differences reported in groups of subjects seen in clinical settings may be caused by referral biases.

Adolescent↗

PubMed2005

A simulated workplace experience for nonmedicated adults with and without ADHD.

Eighteen nonmedicated adults with attention-deficit hyperactivity disorder (ADHD) and 18 who did not have ADHD were evaluated in a full-day simulated workplace experience. It was hypothesized that adults with ADHD would evidence greater impairments on simulated tasks, off-task behavior, and self-reported ADHD symptoms than those without ADHD. Participants were compared on self-reported ADHD symptoms, objective observations, and performance on written tasks. Significant differences were noted in reading comprehension and math fluency as well as observer-rated and self-reported behavior, but not attention. The results of this study suggest that ADHD among adults is associated with significant deficits in performance of workplace tasks, internal experiences, and external observations of core symptoms of ADHD.

Adult↗

PubMed2004

Further evidence of unique developmental phenotypic correlates of pediatric bipolar disorder: findings from a large sample of clinically referred preadolescent children assessed over the last 7 years.

BACKGROUND: A comparison of the prevalence, clinical correlates, and patterns of comorbidity among children with bipolar disorder (BPD) assessed in the early 1990s (1st cohort) with those evaluated over the last 7 years (2nd cohort). METHOD: Subjects in both cohorts were children aged <or=12 years referred to a child psychiatry service and evaluated with identical assessment methods. Children with a DSM-III-R BPD diagnosis (1st cohort, n=43; 2nd cohort, n=129) were identified. For comparison purposes, we used attention-deficit/hyperactivity disorder (ADHD) children without BPD referred to the same clinic during the same time period (1st cohort, n=164; 2nd cohort, n=450). RESULTS: Analogous to 1st cohort findings, 2nd cohort results showed that (1) mania was identified in 17% of subjects; (2) the clinical picture was predominantly irritable and mixed, and the course was chronic; (3) BPD children frequently met criteria for major depression, ADHD, psychosis, and anxiety disorders; and (4) BPD children had high rates of psychiatric hospitalization and had evidence of severely impaired psychosocial functioning. CONCLUSION: These findings confirm that pediatric BPD is a severe clinical disorder afflicting a sizable number of referred preadolescent children. Its unique phenotypic features and patterns of comorbidity support the hypothesis that clinically referred pediatric bipolar disorder represents a very severe developmental subtype of bipolar disorder.

Age of Onset↗

PubMed2004

Meta-analysis of the efficacy of methylphenidate for treating adult attention-deficit/hyperactivity disorder.

This article reviews the efficacy of methylphenidate (MPH) for adult attention-deficit/hyperactivity disorder (ADHD). A literature search identified double-blind placebo-controlled MPH treatment studies of ADHD adults. Meta-analysis estimated the pooled effect size for MPH treatment and tested for publication bias. Meta-analysis regression assessed the influence of study design features on medication effects. Six trials met criteria and were included in this meta-analysis. These studies included a total of 140 MPH-treated ADHD adults and 113 placebo-treated ADHD adults. The mean effect size of 0.9 was statistically significant and there was no evidence of publication bias. Larger MPH effect sizes were associated with physician ratings of outcome and use of higher doses. When treatment is optimized to high doses, the effect size for MPH in adults was 1.3. We found strong support for the assertion that MPH is efficacious for treating adult ADHD. Because the degree of efficacy of MPH in treating ADHD adults is similar to what has been reported from meta-analyses of the child and adolescent literature, our work provides further assurance to clinicians that the diagnosis of ADHD can be validly applied in adulthood.

Adult↗