Plasma cortisol levels in response to a cold pressor test did not predict appetite or ad libitum test meal intake in obese women.

Heightened cortisol response to stress due to hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis may stimulate appetite and food intake. In this study, we assessed cortisol responsivity to a cold pressor test (CPT) as well as appetite ratings and subsequent test meal intake (TMI) in obese women. Following an overnight fast on two counterbalanced days, 20 obese women immersed their non-dominant hand for 2min in ice water (CPT) or warm water (WW) as a control. Plasma cortisol (ng/ml), heart rate, and blood pressure, as well as ratings of stress, pain, and appetite, were serially acquired. An ad libitum liquid meal was offered at 45min and intake measured covertly. Fasting cortisol was higher at 15min (mean peak cortisol) following the CPT compared to WW. Higher stress was reported at 2 and 15min for the CPT compared to WW. Pain, an indirect marker of the acute stress, systolic and diastolic blood pressure increased following the CPT at 2min compared to WW. Hunger decreased after the CPT at 2 and 15min, and desire to eat ratings were lower following CPT compared to WW. Subjects did not have greater test meal intake (TMI) following CPT compared to WW. There was also no significant relationship between cortisol levels following stress and TMI, indicating that cortisol did not predict subsequent intake in obese women.

An open trial of adjunctive donepezil in attention-deficit/hyperactivity disorder.

OBJECTIVE: Despite available pharmacotherapeutics, a number of youths with attentiondeficit/ hyperactivity disorder (ADHD) continue to experience residual symptoms and prominent executive function (EF) deficits resulting in impairment in multiple domains. We sought to determine if donepezil, used adjunctively to stimulant medication, would improve residual symptoms of ADHD and EF deficits. METHODS: In a 12-week open trial, we treated 7 children and 6 adults who had ADHD and evidence of further EF deficits with adjunctive donepezil. All subjects were stabilized on stimulants, at which time donepezil was initiated at 2.5 mg daily and increased to a maximum of 10 mg over the 12-week trial. RESULTS: Of 13 subjects receiving medication, 7 completed the trial. There was no clinically or statistically significant improvement in the ADHD Rating Scale and the Executive Function Checklist, our primary outcome measures. A majority of individuals experienced nonserious adverse events. CONCLUSIONS: Results of this small open study suggest that donepezil augmentation of stimulants is not well tolerated and does not appear useful for the treatment of residual ADHD and/or EF deficits.

Neuropsychological functioning in youth with bipolar disorder.

BACKGROUND: Little is known about the neuropsychological status of youth with bipolar disorder (BPD) or whether cognitive deficits in this population are accounted for by comorbidity with attention deficit/hyperactivity disorder (ADHD). We compared neuropsychological and academic functioning of youth with and without DSM-IV BPD, controlling for effects of comorbid ADHD. METHODS: Fifty-seven youth with BPD and 46 healthy control subjects were assessed on a battery of clinical neuropsychological measures including subtests from the Wechsler Intelligence Scales for Children and Adults (Third Editions), the Stroop, the Wisconsin Card Sorting Test, the Rey-Osterreith Complex Figure, an auditory working memory Continuous Performance Test, a measure of verbal learning, and the Wide Range Achievement Test-Third Edition. RESULTS: Bipolar disorder was associated with impairments on subtests reflecting sustained attention, working memory, and processing speed after controlling for ADHD. Additionally, decrements of moderate effect sizes were found for measures of interference control, abstract problem solving, and verbal learning but did not meet criteria for statistical significance. CONCLUSIONS: After controlling for ADHD, youth with BPD show neuropsychological deficits similar to impairments found in adults with the disorder. Further studies are needed to understand the clinical implications of these impairments as well as their role in the underlying risk for pediatric BPD.

How cardinal are cardinal symptoms in pediatric bipolar disorder? An examination of clinical correlates.

BACKGROUND: The main goal of this study was to test whether the hypothesized cardinal symptom of euphoria results in differences in clinical correlates in bipolar youth ascertained with no a priori assumptions about cardinal symptoms. METHODS: Subjects (n = 86) satisfying DSM-IV criteria for bipolar disorder with and without the proposed cardinal symptom of euphoria were compared in their bipolar symptom pattern, functioning and patterns of comorbidity. RESULTS: Among Criterion A (abnormal mood), we found that severe irritability was the predominant abnormal mood rather than euphoria (94% vs. 51%). We also found that among Criterion B items, grandiosity was not uniquely overrepresented in youth with mania, nor did the rate of grandiosity differ whether irritability or irritability and euphoria were the Criterion A mood symptom. Neither symptom profile, patterns of comorbidity nor measures of functioning differed related to the presence or absence of euphoria. CONCLUSIONS: These findings challenge the notion that euphoria represents a cardinal symptom of mania in children. Instead they support the clinical relevance of severe irritability as the most common presentation of mania in the young. They also support the use of unmodified DSM-IV criteria in establishing the diagnosis of mania in pediatric populations.

Characteristics of adults with attention deficit hyperactivity disorder plus substance use disorder: the role of psychiatric comorbidity.

The objective of the study was to investigate the characteristics of adults with Attention Deficit Hyperactivity Disorder (ADHD) or substance use disorder (SUD), especially in the context of comorbid psychiatric disorders. Subjects were adults (n = 78) participating in a controlled family study of ADHD and SUD. Four groups were identified based on a diagnosis of ADHD or SUD: ADHD, SUD, ADHD + SUD, and neither ADHD nor SUD. All diagnoses were determined by structured clinical interview for DSM IV. Rates of psychiatric comorbidity were lowest in the controls, intermediate in the ADHD and SUD groups, and highest in the ADHD + SUD group. Relative to controls, the ADHD, SUD, and ADHD + SUD groups had higher rates of major depression (z = 1.98, p = 0.05), conduct disorder (z = 2.0, p = 0.04), antisocial personality disorder (z = 2.6, p = 0.009), agoraphobia (z = 2.5, p = 0.01) and social phobia (z = 2.7, p = 0.007). Higher rates of psychiatric comorbidity, especially mood and anxiety disorders, exist in subjects with SUD + ADHD relative to subjects with SUD, ADHD, or controls. Clinicians need to be attentive to other psychiatric disorders that may occur in the large group of adults with ADHD + SUD.

Clinical correlates of bipolar disorder in a large, referred sample of children and adolescents.

OBJECTIVE: To compare the prevalence, clinical correlates, and comorbidity among children and adolescents with bipolar disorder (BPD) assessed in the early 1990s (first cohort) with those evaluated over the last 7 years (second cohort). METHODS: Subjects were consecutively referred children (N=108) and adolescents (N=197) with a DSM-III-R BPD diagnosis, referred to a child psychiatry service and evaluated with identical structured assessment methods. RESULTS: Mania was identified in 16% of referred youth in both age groups and cohorts; in both age groups and cohorts, the clinical picture was predominantly irritable and mixed, and the course was chronic. Youth with BPD in both age groups and cohorts frequently had comorbidity with ADHD, psychosis and anxiety disorders. They also had high rates of psychiatric hospitalization and evidence of severely impaired psychosocial functioning. CONCLUSIONS: The consistency of clinical features of bipolar disorder seen across age groups (children vs. adolescents) and cohorts (early and late cohorts) over the past decade supports the hypothesis that BPD in the young is a severe condition afflicting a sizeable minority of referred youth. These findings replicate and extend our previous characterization of an early onset mania, which may represent a developmental subtype of BPD.

Examining the association between pediatric bipolar disorder and anxiety disorders in psychiatrically referred children and adolescents.

BACKGROUND: To examine the association between anxiety (ANX) and bipolar disorders (BPD) in a clinically referred pediatric sample. METHODS: Subjects were consecutively referred youth aged <18 years, with a DSM-III-R/DSM-IV diagnosis of BPD (n=297) or a disruptive behavior disorder (DBD) (n=1100) on structured interview. RESULTS: Bipolar disorder in youth was associated with a significantly increased risk for most of the DSM-IV anxiety disorders and was not specifically linked to any one disorder in particular. CONCLUSIONS: Bipolar disorder in youth is a significant risk factor for anxiety comorbidity. Considering the morbidity and dysfunction as well as the differing therapeutic needs associated with bipolar and anxiety symptomatology, appropriate therapeutic approaches will be needed for the management of youth with this comorbidity.

Influence of parental SUD and ADHD on ADHD in their offspring: preliminary results from a pilot-controlled family study.

As part of a pilot-controlled family-based study of the children of parents with and without substance use disorders (SUD), the influence of parental SUD and ADHD on the risk for ADHD in offspring was evaluated. Using structured psychiatric interviews, 96 families (183 youth; mean age 11.6 years) were assessed. To evaluate the effect of parental ADHD and SUD, the offspring were stratified into four groups based on parental status: children of parents with neither ADHD nor SUD, children of parents with SUD only, children of parents with ADHD only, and children of parents with both ADHD and SUD. Using generalized estimating equation models, parental SUD and ADHD were used to predict ADHD in the offspring. The rate of children with ADHD increased among children of parents with neither disorder (3%), children of parents with SUD (13%), children of parents with ADHD (25%), and children of parents with both ADHD and SUD (50%) (p = .001). Children of parents with ADHD or ADHD plus SUD were more likely to have ADHD in comparison to children of parents with neither diagnosis (p < 0.05). Children of parents with ADHD plus SUD were at greater risk of ADHD in comparison to children of parents with SUD only (p = 0.01). Despite the small sample size, the results of this study seem to suggest that the offspring of SUD or ADHD parents are at elevated risk for ADHD compared to controls. The offspring of parents with both ADHD and SUD appear to be at the highest risk for ADHD, highlighting the need for careful screening of this group of youth for ADHD. Replication studies clarifying the nature and strength of the association are necessary.

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.

Blood pressure changes associated with medication treatment of adults with attention-deficit/hyperactivity disorder.

OBJECTIVE: To evaluate the effects of medications used in the treatment of adults with attention-deficit/hyperactivity disorder (ADHD) on blood pressure and pulse. METHOD: Subjects were those with DSM-III-R-/DSM-IV-diagnosed ADHD enrolled in placebo-controlled studies of 5 different medications for ADHD. Cardiovascular data from these studies of both stimulants (methylphenidate, amphetamine compounds, pemoline) and nonstimulants (bupropion, desipramine) were reanalyzed for baseline-to-endpoint active-treatment or placebo effects on blood pressure and heart rate. RESULTS: There were 125 subjects with a mean +/- SD age of 39 +/- 9 years. In general, active drug treatment for ADHD compared to baseline was associated with several statistically significant changes in systolic blood pressure (bupropion: +5.9 mm Hg, p < .05 by paired t test; amphetamine: +5.4 mm Hg, p < .05), diastolic blood pressure (desipramine: +7.1 mm Hg, p < .05), and heart rate (bupropion: +6.9 mm Hg, p < .05; amphetamine: +7.3 mm Hg, p < .05; methylphenidate: +4.5 mm Hg, p < .05). New-onset cases of systolic or diastolic hypertension (blood pressure > or = 140/90) were recorded in 8% (7/89) of placebo-treated subjects and 10% (9/89) of subjects receiving active medication, regardless of the class (stimulant, nonstimulant). CONCLUSION: Both stimulant and nonstimulant catecholaminergic medications used in adults with ADHD are associated with minor, but statistically significant, changes in heart rate and blood pressure that were often observed in those receiving placebo. Given the minor pressor and chronotropic effect of these medications, adults with ADHD should have their blood pressure and heart rate checked at baseline and periodically during treatment.

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

The clinical characteristics of unipolar vs. bipolar major depression in ADHD youth.

OBJECTIVE: To investigate the characteristics of unipolar vs. bipolar depression in youth using a sample of children referred for a study on attention deficit hyperactivity disorder (ADHD). METHODS: We compared children with unipolar depression (N=109) to those with bipolar depression (N=43) using boys and girls (N=280) referred for a study on ADHD. Comparisons were made in characteristics of depression, comorbidity and family history. All diagnoses were made using the KSADS-E. RESULTS: In comparison to children with unipolar depression, children with bipolar depression were more likely to have met criteria for depression due to both "sad" and "mad" mood states as stated in the KSADS-E, have severe depression with suicidality, anhedonia and hopelessness. Children with bipolar depression were more likely to have comorbid conduct disorder, severe oppositional defiant disorder, agoraphobia, obsessive compulsive disorder and alcohol abuse, compared to children with unipolar depression. Bipolar depressed children had lower GAF scores and higher rates of hospitalization. Bipolar depression is associated with higher levels of psychiatric disorders in first-degree relatives. CONCLUSIONS: In youth, bipolar depression is distinct from unipolar depression in quality and severity of symptoms, comorbidity and family history. This presentation can aid clinicians in identifying children and adolescents with bipolar disorder.

Absence of gender differences in pediatric bipolar disorder: findings from a large sample of referred youth.

BACKGROUND: Because little is known about gender differences in pediatric bipolar disorder, we evaluated whether gender moderates the expression of pediatric bipolar disorder in a large clinical sample. METHODS: Subjects were consecutively referred youth aged 18 years or less who met full criteria for DSM-III-R bipolar disorder (BPD) (females, n=74; BD males, n=224). All subjects were assessed with a structured diagnostic interview and measures of psychosocial and family functioning. RESULTS: Most of the bipolar subjects (91% of males, 70% of females) also had ADHD. Bipolar disorder was equally prevalent in both genders. Among females and males, severe irritability (83% and 80%, respectively), mixed presentation (87% and 84%, respectively), chronic course (84% and 77%, respectively) and prepubertal onset (78% and 93%, respectively) predominated the clinical picture. We found no meaningful differences between genders in the number of BPD symptoms, type of treatment for BPD (counseling, medication, hospitalization), severity of educational deficits, severity of family and interpersonal functioning or patterns of psychiatric comorbidity. CONCLUSIONS: Because gender does not moderate the clinical expression of pediatric bipolar disorder, our data does not suggest that gender specific criteria for the disorder are warranted.

Risk of substance use disorders in adolescents with bipolar disorder.

OBJECTIVE: Previous work in adults and youths has suggested that juvenile onset bipolar disorder (BPD) is associated with an elevated risk of substance use disorders (SUD). Considering the public health importance of this issue, the authors now report on a controlled study of adolescents with and without BPD to evaluate the risk of SUD. METHOD: Probands with DSM-IV BPD (n=57, mean age +/- SD=13.3 +/- 2.4 years) and without DSM-IV BPD (n=46, 13.6 +/- 2.2 years) were studied. Structured psychiatric interviews and multiple measures of SUD were collected. RESULTS: Bipolar disorder was associated with a highly significant risk factor for SUD (32% versus 7%, Z=2.9, p=.004) that was not accounted for by conduct disorder (adjusted odds ratio=5.4, p=.018). Adolescent-onset BPD (> or =13 years) was associated with a higher risk of SUD compared with those with child-onset BPD (chi1=9.3, p=.002). CONCLUSIONS: These findings strongly indicate that BPD, especially adolescent onset, is a significant risk factor for SUD independently of conduct disorder.

A systematic chart review of the nature of psychiatric adverse events in children and adolescents treated with selective serotonin reuptake inhibitors.

OBJECTIVE: Despite a rapidly growing literature on the efficacy of the selective serotonin reuptake inhibitors (SSRI) in the treatment of juvenile psychiatric disorders, relatively little is described about emotional, behavioral, and cognitive adverse effects associated with their use. To this end we completed a retrospective analysis of medical charts to determine the incidence, nature, and clinical correlates of treatment emergent adverse effects in the behavioral, cognitive, and emotional domains. METHODS: We systematically evaluated the medical charts of children treated with SSRI for depressive or obsessive-compulsive disorders for a mean (+/- SD) of 26.9 + 20.8 months to determine the incidence, nature, and clinical correlates of treatment emergent psychiatric adverse events (PAE). Charts were reviewed for diagnoses, type and dose of SSRI and adjunct medication, specific type of PAE, and time to onset and offset of PAE. RESULTS: In total, 82 charts of children and adolescents (mean age 12.2 +/- 3.2 years) were examined. PAE occurred in 22% of children and were most commonly related to disturbances in mood. PAE were not associated with psychiatric diagnosis(es), age, sex, concurrent medications, doses or specific serotonin reuptake inhibitors. The onset of PAE was observed typically 3 months after SSRI exposure (median = 91 days). Although PAE diminished with SSRI discontinuation, those that emerged early in treatment diminished significantly more rapidly than those that emerged later (median offset was 10 and 49 days, respectively). Re-exposure to an SSRI resulted in another PAE in 44% (n = 18) of the group. CONCLUSION: Based on the retrospective review of medical charts, youth receiving SSRI appear to be at risk for treatment emergent PAE and recurrence with re-exposure to an SSRI. Prospective longer term studies evaluating the course and prognosis of youths manifesting PAE to SSRI are necessary.

Antidepressant use: concordance between self-report and claims records.

BACKGROUND: Researchers need valid methods to assess whether patients are taking their antidepressant medications. Two important sources of data on drug exposure are patients' self-reports and pharmacy claims. OBJECTIVE: To compare self-report and claims data for antidepressant exposure. RESEARCH DESIGN: Cross-sectional analysis. SUBJECTS: This study comprised 422 contemporaneous self-report and claims data points obtained from 164 unique patients in a longitudinal depression study in which patients completed up to five surveys during an 18-month period. MEASURES: For the self-report measure, the following question was asked: Do you now take any prescription medicines for depression? Using claims data, patients were considered to be using an antidepressant if they had filled at least one antidepressant prescription in the 90 days before survey dates. RESULTS: Self-report and claims agreed in 85% (358/422) of cases, with a kappa of 0.69. Eighty-eight percent (56/64) of discrepant cases using other study data sources was resolved. Reasons for discrepancies included the use of medications for conditions other than depression (32/64), recent AD discontinuations (6/64), samples usage (3/64), and low-frequency/PRN use (7/64). CONCLUSIONS: Self-report and claims showed good concordance, but they reflect different truths. Self-report identifies medications intended primarily for the treatment of depressive disorders, whereas claims data identify use of medicines with antidepressant effects. Our assessment of discordant cases showed self-report to be more valid than claims to assess current antidepressant use for depression therapy.